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 biological responses including migration of inflammatory cells, superoxide release, lysosomal enzyme secretion, calcium mobilization, and cellular activation. We previously established that the mouse MHC class I-b molecule H-2M3a binds peptides from the NH2-terminus of the mitochondrially encoded NADH dehydrogenase subunit 1 (ND1). Inasmuch as the N-formyl group is essential for peptide binding both to the chemotactic peptide receptor and to H-2M3a, we sought to test whether ND1 peptides can induce chemotaxis. We now show that fND1(1-12), fND1(1-8), fND1(1-5), fND1(1-4) and fND1(1-3) trigger the chemotactic receptor. Although all tested ND1 peptide derivatives were chemotactic, we found an inverse relationship between peptide length and chemotactic potency (ED50). Our data establish that mitochondrially derived peptides are potent chemotactic ligands. The release of N-formylated peptides 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.
Shawar
S M
SM
Department of Microbiology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.
Rich
R R
RR
Becker
E L
EL
D000595:Amino Acid Sequence; D000818:Animals; D002630:Chemotactic Factors / Q000276:immunology / Q000378:metabolism*; D002633:Chemotaxis / Q000502:physiology*; D051379:Mice; D008928:Mitochondria / Q000201:enzymology / Q000276:immunology*; D008969:Molecular Sequence Data; D009239:N-Formylmethionine / Q000378:metabolism; D009245:NADH Dehydrogenase / Q000276:immunology / Q000378:metabolism*; D009504:Neutrophils / Q000502:physiology*; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D011817:Rabbits; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism; D013329:Structure-Activity Relationship
D002630:Chemotactic Factors; D010446:Peptide Fragments; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D009239:N-Formylmethionine; D009245:NADH Dehydrogenase