Function of phagocytes in experimentally induced colitis in rabbits. I. The Arthus phenomenon in the colon.

Adhesion, random and chemotactic migration, phagocytosis and nitroblue tetrazolium (NBT) dye reduction of peritoneal exudate polymorphonuclear leukocytes (PMN) and macrophages were examined in 110 rabbits with immune complex-mediated colitis and in controls. We may conclude that Arthus-like colitis in rabbits is accompanied by an impairment of adhesion and phagocytosis, and an increase in chemotactic and random migration of both PMN and macrophages. The examined phagocytes were obtained from the peritoneal cavity, and the changes in their function are related much more directly to the presence of circulating immune complexes than to the colitis. The mentioned impairment in their function may be responsible for prolonged persistence of immune complexes in the serum of rabbits with colitis; however, it does not prolong the time of healing of the ulcers.

Normal chemotactic migration of polymorphonuclear leukocytes stimulated with mononuclear-derived chemotactic factor in ulcerative colitis.

The migration of polymorphonuclear leukocytes preincubated with autologous or heterologous serum was examined in 100 patients with untreated ulcerative colitis (UC) and in 100 age- and sex-matched healthy controls. The activity of complement-derived chemotactic factors and mononuclear-derived chemotactic factor (MDCF) was also investigated in the same group of patients. No significant difference was found in random and chemotactic migration of patients or control leukocytes preincubated in different concentrations (10, 50 and 100%) of autologous or heterologous serum. Defective chemotaxis of leukocytes stimulated with complement-derived chemotactic factors was found in UC and was more marked in patients in remission than with active UC independently of whether complement was activated by the alternative or the classical pathway. However, the random migration of neutrophils was enhanced in both groups of UC patients. The leukocytes of patients stimulated with MDCF (mononuclear cells were activated with lipopolysaccharide from Escherichia coli O55:B5) show normal chemotaxis. Our data suggest an impairment of neutrophil receptors for complement-derived chemotactic factor in UC. The decreased response of neutrophils to these factors and normal response to MDCF suggest that the main way in which cells are attracted to the site of inflammation in UC may be a factor produced by stimulated mononuclear cells.

Function of phagocytes in experimentally induced colitis in rabbits. II. The Shwartzman phenomenon in the colon.

Adhesion, phagocytosis, chemotactic and random migration, nitroblue tetrazolium dye reduction of peritoneal exudate neutrophils and macrophages, fibrinogen level, gelation of soluble fibrin and serial dilution protamine sulfate test were investigated in 115 New Zealand white rabbits with experimentally induced Shwartzman phenomenon in the colon, and in control animals. The results presented in this report demonstrated impairment of chemotactic migration of phagocytes in the presence of endotoxin. The depression was dose-dependent and less marked when neutrophils were stimulated with monocyte-derived chemotactic factor or with casein, than with complement-derived chemotactic factor. The prolonged depression of chemotactic migration of neutrophils and macrophages in rabbits with colitis, however, did not affect the healing time of the ulcers in the colon.

Modulatory effect of the gut on. Polymorphonuclear leukocytes motility. Preliminary report.

We have compared the spontaneous and stimulated motility of PMN from blood samples taken simultaneously from human portal and cubital vein. Blood was taken during laparotomy from 10 cholecystectomized patients and from 6 patients in whom carcinoma of pancrease was confirmed. In all subjects both spontaneous and stimulated migration rates of PMN from the portal vein were lower than that of PMN isolated from the cubital vein; the differences were significant. We conclude that the gut probably modulates the motility of PMN.

Inhibition of human leukocyte locomotion by tilorone hydrochloride and by RMI 9563 DA measured in vitro.

The effect of tilorone hydrochloride and RMI 9563 DA on neutrophil locomotion was studied in experimental conditions. It was shown that depression of random and stimulated migration and of chemotaxis increased with rising concentration of these drugs.

Humoral immune system and ulcerative colitis activity. I. Serum immunoglobulins and C-reactive protein levels.

Serum immunoglobulins and C-reactive protein (CRP) levels were examined in 85 ulcerative colitis (UC) patients and were correlated with activity, extension and duration of the disease, as well as with extraintestinal manifestations and therapeutic effects. An increase of IgG, IgA, IgM, IgE, CRP and decrease of IgD levels was found in UC, but the activity of the disease was correlated only with CRP level. Patients with extraintestinal manifestations showed elevation of IgG, IgA and IgM level, however, only in inactive colitis. After 12 months of therapy with sulphasalazine the immunoglobulins and CRP returned to the level found in the inactive colitis. An elevation of IgE level was also observed in patients with accompanying allergic disorders. The examined parameters did not reveal any relationship with the duration or extension of the disease. It seems that abnormality in immunoglobulin and CRP levels is an accompanying phenomenon in UC. Increase of IgE level suggests the share of allergic mechanism in pathogenesis of the disease.

Humoral immune system and ulcerative colitis activity. II. Complement level.

C4, C3 and C5 levels and the complement hemolytic activity were analysed in 84 ulcerative colitis patients and correlated with activity, extension and duration of the disease, with the presence of extraintestinal manifestation, and with therapeutic effects. The elevation of C3 was observed in both mild active and in severe colitis. Only C3 correlated with disease activity and with C-reactive protein level. On the other hand, C4 and C5 levels were significantly decreased in the active disease extended to the left side or to total great bowel. The importance of these findings is discussed. No significant connection of the examined complement components with duration, therapy and extraintestinal manifestation was observed. A trend to increase the complement hemolytic activity in severe colitis was noted. Our study of complement and its components activity suggests the secondary role of analysed parameters in pathogenesis of UC and clinical usefulness of C3 level as an indicator of the disease activity.

The neutrophil function and infectious diseases in workers occupationally exposed to organochloride insecticides.

The function of polymorphonuclear leucocytes (PMNs) was examined in 33 workers with occupational exposure to organochloride insecticides. A deep impairment of chemotaxis, adhesion, phagocytosis and nitroblue tetrazolium-dye reduction was found. A simultaneous increase of random migration and stimulated migration was observed. Perhaps the increase of the surface migration of leucocytes can partially compensate for the decrease of chemotaxis. However, no correlation between chemotaxis and spontaneous or stimulated migration could be demonstrated. The failure of PMN incubation in autologous serum to affect leucocyte migration and the fact that chemo-attractant generated from the plasma of both workers and controls show similar activity both suggest that the damaged PMN chemotaxis is not serum but cell-dependent. The simultaneous increase of infectious disease, especially of the upper respiratory tract, was found in the group of workers chronically exposed to organochloride insecticides. This kind of infection in the examined group of workers depends mainly on the chronic exposure to insecticides and only partially on the observed impairment of leucocyte function. A possible cause for the frequency of infections in workers is discussed.

Chemotaxis and random migration of polymorphonuclear leukocytes in ulcerative colitis examined by the agarose method.

Chemotaxis and random migration of neutrophils under agarose were compared between untreated ulcerative colitis patients (35 women and 36 men) and healthy subjects (25 women and 28 men). The ulcerative colitis patients were divided into two subgroups--those with the active (no. = 41) and those with the inactive (no. = 30) stage of the disease. High spontaneous mobility and subnormal chemotaxis (both aberrations statistically significant) were noted in the ulcerative colitis patients. Polymorphonuclear leukocyte chemotaxis was significantly lower in inactive than in active colitis. Possible causes of the difference in neutrophil chemotaxis between the two disease groups were discussed. No difference in the chemotactic activity between zymosan-stimulated plasma from controls and patients was found. The defect in the chemotaxis of neutrophils in ulcerative colitis might explain the small abscesses persisting in the mucosa of the great bowel.