Neutrophil emigration in the lungs, peritoneum, and skin does not require gelatinase B

Polymorphonuclear leukocytes (PMN) release gelatinase B in response to vari able stimuli. Gelatinase B degrades basement membrane components in vitro, and inhibition of matrix metalloproteinase activity blunts PMN migration th rough a prototype basement membrane (Matrigel) and amnionic membranes, Acco rdingly, it has been speculated that gelatinase B is necessary for PMN emig ration. 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: per itoneal cavity 4 h after thioglycollate-induced peritonitis was also compar able in gelatinase B-/- and gelatinase B+/+ mice. At 3 h after an intraderm al injection of interleukin-8, numerous PMN were present extravascularly in the dermis in both gelatinase B-/- and gelatinase B+/+ mice and the myelop eroxidase activities of the skin at the injection sites were indistinguisha ble between the two types of mice. PMN from gelatinase B-/- mice migrated t hrough Matrigel in response to zymosan-activated serum with thr: same effic iency as did PMN from gelatinase B+/+ mice. In vitro, gelatinase B-/- PMN k illed Staphylococcus aureus and Klebsiella pneumoniae as effectively as did PMN from gelatinase B+/+ mice. These findings indicate that gelatinase B i s not required for PMN emigration, and suggest that the antibacterial funct ion of PMN is preserved despite gelatinase B deficiency.