Suppression of polymorphonuclear leucocyte chemotaxis by Pseudomonas aeruginosa elastase in vitro: a study of the mechanisms and the correlation with ring abscess in pseudomonal keratitis.
Bacteria, or the culture supernatants of an elastase non-producing strain of Pseudomonas aeruginosa, elicited a chemotactic response from polymorphonuclear leucocytes (PMN) in vitro. The chemoattractive capacity was diminished under the presence of Boc-Phe-Leu-Phe-Leu-Phe, a receptor antagonist of N-formyl-Met-Leu-Phe (fMLP) which is a bacterial chemotactic peptide to PMN. This indicated that the chemoattractant derived from Pseudomonas aeruginosa was a fMLP-like molecule(s). In contrast, culture supernatants of an elastase producing strain of Pseudomonas aeruginosa produced negligible chemotactic response from PMN. Indeed, an inhibitory effect of the culture supernatants or of purified Pseudomonas aeruginosa elastase (PAE) on PMN chemotaxis was observed when fMLP was used as a chemoattractant. Another fMLP-induced function of PMN, respiratory burst activation, was also diminished by pretreatment of PMN with PAE. PAE hydrolysed fMLP at the Met-Leu bond and diminished the chemoattractant capacity. In addition, a receptor analysis with fML-3H-P demonstrated a decrease in numbers of fMLP receptors on PMN without changing the dissociation constant values after the treatment of the cells with PAE. In the primary structure of the fMLP receptor previously reported, a preferential amino acid sequence for cleavage by PAE was identified in what was believed to be an extracellular portion of the receptor molecule. These results suggested that PAE could diminish PMN infiltration in response to Pseudomonas aeruginosa in vivo by cleavage of the fMLP-like pseudomonal chemotactic ligand and the receptors on PMN.
Ijiri
Y
Y
Department of Ophthalmology, School of Medicine, Kumamoto University, Japan.
Matsumoto
K
K
Kamata
R
R
Nishino
N
N
Okamura
R
R
Kambara
T
T
Yamamoto
T
T
D000038:Abscess / Q000201:enzymology*; D001426:Bacterial Proteins; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D017077:Culture Media, Conditioned; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects; D007634:Keratitis / Q000201:enzymology*; D008666:Metalloendopeptidases / Q000494:pharmacology*; D008954:Models, Biological; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology; D011552:Pseudomonas Infections / Q000201:enzymology; D011550:Pseudomonas aeruginosa / Q000145:classification / Q000201:enzymology*; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000187:drug effects; D018000:Receptors, Peptide / Q000187:drug effects
D001426:Bacterial Proteins; D017077:Culture Media, Conditioned; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D009240:N-Formylmethionine Leucyl-Phenylalanine; D008666:Metalloendopeptidases; C043859:pseudolysin, Pseudomonas aeruginosa