STRUCTURAL CHARACTERIZATION OF BPI-MODULATING 15 KDA PROTEINS FROM RABBIT POLYMORPHONUCLEAR LEUKOCYTES - IDENTIFICATION OF A NOVEL FAMILY OF LEUKOCYTE PROTEINS

We have previously described the isolation and initial characterizatio n of 15 kDa protein isoforms (p15s) from rabbit polymorphonuclear leuk ocytes (PMN) that bind to Escherichia coli and modulate the antibacter ial actions of other leukocyte proteins on this gram negative organism . We now report that the p15s differ in primary structure. The cloning and sequencing of two distinct p15 cDNAs from a rabbit bone marrow li brary reveal that two of the isoforms are closely similar in primary s tructure differing at only two amino acid positions. The p15 cDNAs enc ode putative signal sequences suggesting a granule-associated localiza tion for these proteins. Analysis of the derived p15 primary structure s reveals homology to two leukocyte proteins: CAP-18, an 18 kD lipopol ysaccharide (LPS) binding protein from rabbit PMN and cathelin, an 11 kD cysteine protease inhibitor from porcine leukocytes. This structura l similarity suggests the existence of a novel family of low molecular weight leukocyte proteins with potential roles in inflammation.