Lawrence Paulraj K, Srikumaran Subramaniam
Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USA.
Vet Immunol Immunopathol. 2007 Oct 15;119(3-4):287-98. doi: 10.1016/j.vetimm.2007.05.019. Epub 2007 Jun 3.
Leukotoxin (Lkt) is the primary virulence factor secreted by Mannheimia haemolytica which causes pneumonia in ruminants. Previously, we have shown that CD18, the beta subunit of beta(2) integrins, mediates Lkt-induced cytolysis of ruminant leukocytes. CD18 associates with four distinct alpha subunits giving rise to four beta(2) integrins, CD11a/CD18 (LFA-1), CD11b/CD18 (Mac-1), CD11c/CD18 (CR4), and CD11d/CD18. It is not known whether all the beta(2) integrins serve as a receptor for Lkt. Since PMNs are the leukocyte subset that is most susceptible to Lkt, and Mac-1 expression on PMNs exceeds that of other beta(2) integrins, it is of interest to determine whether Mac-1 serves as a receptor for Lkt which necessitates the cloning of CD11b and CD18. In this study, we cloned and sequenced the cDNA encoding CD11b of Ovis canadensis (bighorn sheep) and Ovis aries (domestic sheep). CD11b cDNA is 3455 nucleotides long encoding a polypeptide of 1152 amino acids. CD11b polypeptides from these two species exhibit 99% identity with each other, and 92% with that of cattle, and 70-80% with that of the non-ruminants analyzed.
白细胞毒素（Lkt）是溶血曼氏杆菌分泌的主要毒力因子，可导致反刍动物肺炎。此前，我们已经表明，β2整合素的β亚基CD18介导Lkt诱导的反刍动物白细胞细胞溶解。CD18与四个不同的α亚基结合，产生四种β2整合素，即CD11a/CD18（淋巴细胞功能相关抗原-1）、CD11b/CD18（巨噬细胞-1抗原）、CD11c/CD18（补体受体4）和CD11d/CD18。目前尚不清楚所有的β2整合素是否都作为Lkt的受体。由于中性粒细胞是对Lkt最敏感的白细胞亚群，且中性粒细胞上Mac-1的表达超过其他β2整合素，因此确定Mac-1是否作为Lkt的受体很有意义，这需要克隆CD11b和CD18。在本研究中，我们克隆并测序了加拿大盘羊（大角羊）和绵羊（家羊）编码CD11b的cDNA。CD11b cDNA长3455个核苷酸，编码一个由1152个氨基酸组成的多肽。这两个物种的CD11b多肽彼此间具有99%的同一性，与牛的同一性为92%，与所分析的非反刍动物的同一性为70-80%。
