ABSTRACT
Mannheimiosis is the major respiratory disease among some ruminants, whereas it is not pathogenic for other mammals, an observation that has been attributed to a specific interaction between Mannheimia haemolytica leukotoxin (Lkt) and bovine or ovine CD18 subunit of lymphocyte function-associated antigen-1 (LFA-1) and Mac-1. We therefore hypothesized that Lkt utilizes CD18 as its receptor on caprine leukocytes as well. We have transiently transfected the beta2-integrins-deficient K-562 cell line with cDNAs encoding caprine CD11a and caprine CD18 to determine the susceptibility of the transfectants to Lkt-induced cytolysis. Flow cytometric analysis of the transfectants revealed surface expression of caprine LFA-1 and lysis by Lkt in a concentration-dependent manner whereas the parent cells were not. Moreover, K562 cells expressing caprine CD18 and human or bovine CD11a were also sensitive to Lkt whereas K-562 cells expressing caprine CD11a and human CD18 were not. Taken together, these results indicate that CD18 on caprine leukocytes serves as a receptor for Lkt.
Subject(s)
CD18 Antigens/immunology , Cytotoxins/immunology , Exotoxins/immunology , Leukocytes/immunology , Mannheimia haemolytica/immunology , Animals , Bacterial Toxins/genetics , Bacterial Toxins/immunology , Bacterial Toxins/isolation & purification , CD11 Antigens/genetics , CD11 Antigens/immunology , CD18 Antigens/genetics , Cattle , Cell Line , Cytotoxins/genetics , Cytotoxins/isolation & purification , Exotoxins/genetics , Exotoxins/isolation & purification , Goat Diseases/immunology , Goat Diseases/microbiology , Goats , Humans , Lymphocyte Function-Associated Antigen-1/genetics , Lymphocyte Function-Associated Antigen-1/immunology , Mannheimia haemolytica/genetics , Mannheimia haemolytica/pathogenicity , Pasteurellaceae Infections/immunology , Pasteurellaceae Infections/microbiology , Pasteurellaceae Infections/veterinary , Protein BindingABSTRACT
Mucinous epithelial ovarian cancers (MOC) are clinically and morphologically distinct from the other histological subtypes of ovarian cancer. To determine the genetic basis of MOC and to identify potential tumour markers, gene expression profiling of 49 primary ovarian cancers of different histological subtypes was performed using a customised oligonucleotide microarray containing >59 000 probesets. The results show that MOC express a genetic profile that both differs and overlaps with other subtypes of epithelial ovarian cancer. Concordant with its histological phenotype, MOC express genes characteristic of mucinous carcinomas of varying epithelial origin, including intestinal carcinomas. Differences in gene expression between MOC and other histological subtypes of ovarian cancer were confirmed by RT-PCR and/or immunohistochemistry. In particular, galectin 4 (LGALS4) was highly and specifically expressed in MOC, but expressed at lower levels in benign mucinous cysts and borderline (atypical proliferative) tumours, supporting a malignant progression model of MOC. Hence LGALS4 may have application as an early and differential diagnostic marker of MOC.
