Neutrophil emigration in the lungs, peritoneum, and skin does not require gelatinase B.
Polymorphonuclear leukocytes (PMN) release gelatinase B in response to variable stimuli. Gelatinase B degrades basement membrane components in vitro, and inhibition of matrix metalloproteinase activity blunts PMN migration through a prototype basement membrane (Matrigel) and amnionic membranes. Accordingly, it has been speculated that gelatinase B is necessary for PMN emigration. To test this hypothesis we induced acute inflammation in the lungs, peritoneum, and skin in mice with a null mutation of the gelatinase B gene (gelatinase B-/-) and littermate controls (gelatinase B+/+). At 3, 6, 12, and 24 h after intratracheal instillation of LPS, the emigration of PMN in the lung, as determined by PMN in bronchoalveolar lavage fluid, was similar in gelatinase B-/- and gelatinase B+/+ mice. The number of PMN in the peritoneal cavity 4 h after thioglycollate-induced peritonitis was also comparable in gelatinase B-/- and gelatinase B+/+ mice. At 4 h after an intradermal injection of interleukin-8, numerous PMN were present extravascularly in the dermis in both gelatinase B-/- and gelatinase B+/+ mice and the myeloperoxidase activities of the skin at the injection sites were indistinguishable between the two types of mice. PMN from gelatinase B-/- mice migrated through Matrigel in response to zymosan-activated serum with the same efficiency as did PMN from gelatinase B+/+ mice. In vitro, gelatinase B-/- PMN killed Staphylococcus aureus and Klebsiella pneumoniae as effectively as did PMN from gelatinase B+/+ mice. These findings indicate that gelatinase B is not required for PMN emigration, and suggest that the antibacterial function of PMN is preserved despite gelatinase B deficiency.
Betsuyaku
T
T
Pulmonary and Critical Care Medicine, Department of Medicine, Barnes-Jewish Hospital at Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Shipley
J M
JM
Liu
Z
Z
Senior
R M
RM
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002465:Cell Movement; D017364:Collagenases / Q000172:deficiency* / Q000502:physiology*; D007249:Inflammation; D008168:Lung / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9; D051379:Mice; D008822:Mice, Transgenic; D009504:Neutrophils / Q000502:physiology*; D010537:Peritoneum / Q000378:metabolism*; D012867:Skin / Q000033:anatomy & histology / Q000378:metabolism*; D013997:Time Factors
D017364:Collagenases; D020780:Matrix Metalloproteinase 9