PEPTIDES FROM THE AMINO-TERMINUS OF MOUSE MITOCHONDRIALLY ENCODED NADH DEHYDROGENASE SUBUNIT-1 ARE POTENT CHEMOATTRACTANTS

Binding of N-formylated chemotactic peptides to specific cell surface receptors on polymorphonuclear leukocytes initiates a wide range of bi ological responses including migration of inflammatory cells, superoxi de release, lysosomal enzyme secretion, calcium mobilization, and cell ular activation. We previously established that the mouse MHC class I- b molecule H-2M3(a) binds peptides from the NH2-terminus of the mitoch ondrially encoded NADH dehydrogenase subunit 1 (ND1). Inasmuch as the N-formyl group is essential for peptide binding both to the chemotacti c peptide receptor and to H-2M3(a), we sought to test whether ND1 pept ides can induce chemotaxis. We now show that fND1(1-12), fND1(1-8), fN D1(1-6), fND1(1-5), fND1(1-4) and fND1(1-3) trigger the chemotactic re ceptor. Although all tested ND I peptide derivatives were chemotactic, we found an inverse relationship between peptide length and chemotact ic potency (ED(50)). Our data establish that mitochondrially derived p eptides are potent chemotactic ligands. The release of N-formylated pe ptides from disintegrating mitochondria may play an important role in the inflammatory response resulting from tissue injury. By attracting the host phagocytic cells to sites of tissue breakdown, these peptides could mediate an essential first step in tissue repair and healing. ( C) 1995 Academic Press, Inc.