Ganz T, Rayner J R, Valore E V, Tumolo A, Talmadge K, Fuller F
Will Rogers Institute of Pulmonary Research, UCLA, Los Angeles, CA 90024-1736.
J Immunol. 1989 Aug 15;143(4):1358-65.
Defensins are a family of microbicidal and cytotoxic peptides abundant in the lysosomal granules of mammalian phagocytes. We present the cDNA and genomic sequences of two rabbit defensins, macrophage cationic peptides MCP-1 and MCP-2. Their cDNA and genomic sequences are highly homologous, reflecting the homology between the two defensins (32 of 33 amino acids). The MCP genes are closely linked (within 13 kb) suggesting that they evolved by a recent tandem gene duplication. Their cDNA sequences indicate that the peptides are synthesized as 95 amino acid prepro-MCPs, consistent with their lysosomal location. The MCP genes are separated into three exons encoding distinct domains: the 5' untranslated region, the prepropeptide domain, and the mature defensin sequence. Fully developed polymorphonuclear leukocytes, short-lived phagocytes with limited capacity for protein and nucleic acid synthesis, contained MCPs but lacked MCP mRNA. MCP mRNA was found in bone marrow and spleen, organs which contained immature polymorphonuclear leukocytes. MCP and MCP mRNA were detected in lung macrophages, but not in macrophages from other organs, nor in monocytes, the putative macrophage precursors. In macrophages, the expression of MCPs appears to be a marker of lung-specific differentiation.
防御素是一类在哺乳动物吞噬细胞的溶酶体颗粒中大量存在的杀微生物和细胞毒性肽。我们展示了两种兔防御素——巨噬细胞阳离子肽MCP-1和MCP-2的cDNA和基因组序列。它们的cDNA和基因组序列高度同源，反映了这两种防御素之间的同源性（33个氨基酸中有32个相同）。MCP基因紧密相连（在13 kb范围内），表明它们是通过近期的串联基因复制进化而来的。它们的cDNA序列表明这些肽是以95个氨基酸的前原MCP形式合成的，这与其溶酶体定位一致。成熟的多形核白细胞是蛋白质和核酸合成能力有限的短命吞噬细胞，含有MCP，但缺乏MCP mRNA。在骨髓和脾脏中发现了MCP mRNA，这些器官含有未成熟的多形核白细胞。在肺巨噬细胞中检测到了MCP和MCP mRNA，但在其他器官的巨噬细胞中未检测到，在单核细胞（假定的巨噬细胞前体）中也未检测到。在巨噬细胞中，MCP的表达似乎是肺特异性分化的一个标志。
