Effects of alpha 1-proteinase inhibitor on chemotaxis and chemokinesis of polymorphonuclear leukocytes: its possible role in regulating polymorphonuclear leukocyte recruitment in human subjects.
A variety of biologic products derived from bacteria, inflammatory cells, and active degraded proteins have been identified as having chemotactic activity essential for polymorphonuclear leukocyte (PMN) recruitment to the site of inflammation. Little is known, however, concerning factors responsible for regulating the intensity and duration of PMN recruitment. Evidence is growing that proteinase inhibitors modify the migrating ability of PMNs, although the physiologic implications of this have eluded clarification. In an attempt to hypothesize a role of alpha 1-proteinase inhibitor (alpha 1-Pi) in PMN recruitment to inflammatory sites, we examined the effects of alpha 1-Pi in different physiologic concentrations on PMN migration with a microchemotaxis chamber technique. Alpha 1-proteinase inhibitor had both stimulatory and inhibitory effects on cell migration, depending on its concentration. The inhibitor was active in inducing both directed locomotion (chemotaxis) and nondirected locomotion (chemokinesis) in concentrations of 0.02, 0.2, and 2 mg/ml, with maximum potency in both cases at 0.2 mg/ml (corresponding to the normal alveolar surface fluid level in the lung). Alpha 1-proteinase inhibitor impaired chemotactic responsiveness to known chemoattractants at 2 and 10 mg/ml (corresponding to normal and inflammatory blood levels, respectively) in order of potency. These results suggest that alpha 1-Pi may play a role in regulating inflammatory processes, especially in the lung, through its stimulatory and inhibitory effects, depending on its concentration.
Aoshiba
K
K
First Department of Medicine, Tokyo Women's Medical College, Japan.
Nagai
A
A
Ishihara
Y
Y
Kagawa
J
J
Takizawa
T
T
D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D015936:Complement C5a / Q000494:pharmacology; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology*; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000515:alpha 1-Antitrypsin / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D000515:alpha 1-Antitrypsin; D014108:Tosylphenylalanyl Chloromethyl Ketone; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a