Role of pulmonary macrophages in resistance to experimental metastasis.

Intranasal inoculation of C3H/HeN mice with Propionibacterium acnes activates pulmonary macrophages but not splenic or peritoneal macrophages. When mice so treated were injected IV with tumor cells, no protection against the challenge was seen. Conversely, inoculation of C3H/HeN mice with P. acnes by the IP route activated splenic and peritoneal macrophages but not pulmonary macrophages. When mice with activated splenic and peritoneal macrophages were challenged with an IV injection of tumor cells, the mice demonstrated an increased resistance to the formation of pulmonary tumors. Thus, activation of splenic and peritoneal macrophages correlated better with protection against IV tumor challenge than activation of pulmonary macrophages. Experiments were done that demonstrated that the effect was not due to the augmentation of NK cell activity. The data are consistent with the conclusion that activated pulmonary macrophages alone are not effective in conferring resistance to pulmonary tumor nodule formation in this tumor model.

Suppressive effects of 3-methylcholanthrene on the in vitro antitumor activity of naturally cytotoxic cells.

Transient suppression of splenic natural killer (NK), natural cytotoxic (NC), and peritoneal macrophage cytotoxicity was observed following a single injection of 3-methylcholanthrene (3-MC) into C3H/HeN mice. Natural killer cell activity was depressed by 30-60% 4-6 d after injection of 1.0 mg 3-MC. Levels of NK reactivity returned to normal 8 d post 3-MC injection, and no suppression of natural killing was seen when tested 6 wk after 3-MC treatment. 3-MC did not affect Propionibacterium acnes augmentation of NK cell activity when tested both 6 d and 6 wk after carcinogen injection. The results indicate that the observed suppression of naturally cytotoxic cells may not be important in allowing 3-MC-induced tumors to grow, since suppression is not long-lasting. Therefore, any effect on tumor growth mediated by a suppression of naturally cytotoxic cells would have to be exerted at the earliest stages of tumor development.

Immune response to ultraviolet-induced tumors. I. Transplantation immunity developing in syngeneic mice in response to progressor ultraviolet-induced tumors.

Ultraviolet-light-induced murine skin tumors were analyzed for the ability to induce transplantation immunity and cytotoxic lymphocytes in syngeneic mice. A correlation was found between tumor regression and the induction of cytotoxic T cells with specificity for a unique tumor-associated antigen. Processing tumors possessed tumor-associated transplantation antigens (TATA), which could be demonstrated by transplantation in hyperimmunized mice. Progression correlated with a lack of splenic cytotoxic T cell reactivity. High levels of in situ cytotoxic reactivity could be induced by presenting the tumor-specific antigen on nongrowing tumor cells. Tumor-bearer hosts were shown to be sensitized to TATA because cultured tumor-bearer T cells adoptively transferred protection against tumor outgrowth. Mechanisms of the in vivo suppression of antitumor immunity are discussed.

Experimental uveitis. Elicited by peptidoglycan-polysaccharide complexes, lipopolysaccharide, and muramyl dipeptide.

Uveitis could be a reaction to bacterial debris disseminated to the eye from extraocular sites of infection. In this study, we relate the composition of several bacterial components to their inflammatory properties in the eye. Groups of rabbits were injected intravitreously with peptidoglycan-polysaccharide (PG-PS) complexes isolated from group A streptococci, Escherichia coli lipopolysaccharide (LPS), or synthetic muramyl dipeptide (MDP). The lipid A region of LPS and the glycan backbone of PG are chemical analogues; MDP is the minimal biologically active subunit of PG. All of these molecules elicited uveitis as observed both clinically and histologically. The MDP elicited an acute inflammation characterized by a heterophil and monocyte infiltrate that subsided within 16 days. The PG-PS and LPS elicited chronic inflammation characterized by mononuclear and lymphocyte infiltration and severe necrosis of the retina.

Latent period and antigenicity of murine tumors induced in C3H mice by short-wavelength ultraviolet radiation.

Skin tumors were induced in C3H/HeNCr1BR mice with chronic short-wavelength ultraviolet (UVC) irradiation using a germicidal lamp (254 nm). Fifty percent of mice had developed tumors by 9 1/2 months (range 8-12 months). With progressive irradiation, mice developed multiple tumors on the back reaching a mean of 2.9 tumors/mouse at 11 1/2 months. No tumors developed on the ears. Of 83 lesions examined histologically 66 (80%) were squamous cell carcinomas, 6 (7%) were fibrosarcomas, and 10 (12%) were proliferative squamous lesions without evident invasion. Twenty-two squamous cell carcinomas were transplanted s.c. into normal syngeneic mice and into mice immunosuppressed by adult thymectomy, lethal x-irradiation, and bone marrow or neonatal liver reconstitution. Transplantation of squamous cell carcinomas was successful in a total of 17/22 (77%) cases. Only 11/22 (50%) tumors grew progressively in normal mice. Six of 22 (27%) tumors grew progressively in immunosuppressed mice but not normal syngeneic recipients. Three fibrosarcomas were also transplanted. All 3 grew progressively in immunosuppressed hosts but failed to grow in normal syngeneic recipients. Two fibrosarcomas that were induced by a germicidal lamp were found to grow significantly better in UVB-irradiated (280-320 nm) mice than in normal mice. Conversely, a UVB-induced fibrosarcoma showed enhanced growth in UVC-irradiated mice compared to growth in normal, age-matched controls.

Specific attachment of collagen to cardiac myocytes: in vivo and in vitro.

The formation and attachment of collagen to the sarcolemma of cardiac myocytes were examined in vivo in neonatal rats and hamsters and in vitro in cultures of neonatal rat myocytes. Scanning, transmission, and high-voltage electron microscopy were used to show that the collagen struts attach to specific sites on the sarcolemma just lateral to the Z band of neonatal animals. In vitro, collagen preferentially attaches to distal end of myocytes at a site where internal stress fibers also attach to the sarcolemma. Formation of the collagen struts appeared to be a multistep process involving several components of the extracellular matrix. The role of the collagen struts is involved in the distribution of force generated by muscle contraction.

Further characterization of immunological unresponsiveness induced in mice by ultraviolet radiation. Growth and induction of nonultraviolet-induced tumors in ultraviolet-irradiated mice.

Ultraviolet (UV)-irradiated mice were compared with unirradiated mice for their susceptibility to primary and transplanted tumors etiologically unrelated to UV radiation. Although UV-irradiated mice are unable to reject transplants of highly antigenic syngeneic tumors induced by UV light, the growth of syngeneic, non-UV-induced tumors generally was not accelerated in these animals. Furthermore, UV-irradiated mice were no more susceptible to the induction of primary leukemias, mammary tumors, or sarcomas than were unirradiated animals. Tests of immune responses to weak transplantation antigens showed that UV-irradiated mice rejected H-Y-incompatible skin grafts as vigorously as did normal animals, and that the primary in vitro cytotoxic responses of spleen cells from UV-irradiated mice to trinitrophenyl (TNP)-modified syngeneic cells and to Hh antigens were unaffected. We conclude that the susceptibility of UV-irradiated mice to challenge with UV-induced tumors represents a selective unresponsiveness, and that it is not attributable to a generalized deficiency in the immune response to tumor-specific antigens or to weak transplantation antigens.

Distribution of H antigen in persons of blood groups A, B, and AB.

The distribution of H antigen in tissues of persons of blood groups A, B, and AB was examined. H antigen could be demonstrated in all tissues in which the isologous antigens A and B were demonstrated, although some cells demonstrated isologous but not H antigen. In most tissues, areas were seen that demonstrated H antigen but not the isologous antigen. This was especially true in Brunner's glands of the duodenum and esophageal glands, where the amount of H antigen was apparently greater than the amount of the isologous antigen. Since the results varied greatly from tissue to tissue, it was not possible to interpret the data with respect to the biochemical pathways of blood group antigen formation.

Identification and cytotoxic reactivity of inflammatory cells recovered from progressing or regressing syngeneic UV-induced murine tumors.

Most tumors induced in C3H mice by ultraviolet (UV) light are immunologically rejected by normal syngeneic recipients, but will grow progressively in immunosuppressed mice and in mice treated with UV light. In this study we compared the composition and cytotoxic activity of the inflammatory cell infiltrate from tumors transplanted into syngeneic UV-irradiated or unirradiated mice. Tumor fragments were implanted in either normal (regressor) or UV-treated (progressor) mice, and removed on various days after implantation and mechanically dissociated. The cells were examined by immunofluorescence for theta and immunoglobulin markers, stained for morphologic examination, and tested for cytotoxicity against the tumor. No significant differences were noted in numbers of macrophages, granulocytes, or B cells recovered from progressing or regressing tumors on day 6, the time of greatest activity. However, the numbers of T cells recovered from tumor fragments implanted in normal mice was approximately 3-fold that recovered from tumor fragments implanted in UV-treated mice. Lymphocytes recovered from regressing tumor fragments were specifically cytotoxic for that tumor in a microcytotoxicity test; those from progressing tumor fragments were not cytotoxic.

Accelerated growth of syngeneic tumors in mice treated with methylcholanthrene.

BALB/c and C3H- mice were given a single injection of methylcholanthrene (MCA) and were tested at various times thereafter for immunologic reactivity and resistance to syngeneic tumor challenge. MCA treatment did not affect the rejection of H-2-incompatible tumor allografts, the rejection of H-2-compatible skin allografts, or the induction of delayed hypersensitivity to DNCB as measured by footpad challenge. In contrast, mice treated with MCA exhibited an increase susceptibility to challenge with several syngeneic ultraviolet-induced and MCA-induced fibrosarcomas. These studies demonstrate that in the autochthonous host the measurement of host immune status by in vivo cell-mediated immune responses to exogenous antigens does not necessarily predict the host response to tumor growth.

Isoantigen ABH in cervical intraepithelial neoplasia.

The purpose of the study was to examine the relationship between the histologic findings and the presence or absence of ABH isoantigens in intraepithelial neoplasia of the cervix. After the lesions were graded by four pathologists, the Red Cell Adherence (RCA) test was done to demonstrate the ABH antigens, and the results of the two were compared. The correlation between the morphologic diagnosis and the results of the RCA test was limited. The percentages of tissues giving positive (+) or positive-negative (+/-) reactions were very similar in intraepithelial neoplsia (59.2%) and normal squamous epithelium (58.4%). The relationship of the RCA test results and behavior of the lesion was not studied.