Expression of human group II PLA2 in transgenic mice results in epidermal hyperplasia in the absence of inflammatory infiltrate.

Abstract

Group II PLA 2 has been implicated in inflammatory processes in both man and other animals and has been shown to be involved in inflammatory conditions, such as arthritis and sepsis. Transgenic mice expressing the human group II PLA 2 gene have been generated using a 6.2-kb genomic fragment. These mice express the group II PLA 2 gene abundantly in liver, lung, kidney, and skin, and have serum PLA 2 activity levels approximately eightfold higher than nontransgenic littermates. The group II PLA 2 transgenic mice reported here exhibit epidermal and adnexal hyperplasia, hyperkeratosis, and almost total alopecia. The chronic epidermal hyperplasia and hyperkeratosis seen in these mice is similar to that seen in a variety of dermatopathies, including psoriasis. However, unlike what is seen with these dermatopathies, no significant inflammatory-cell influx was observed in the skin of these animals, or in any other tissue examined.

Platelet microparticles are internalized in neutrophils via the concerted activity of 12-lipoxygenase and secreted phospholipase A 2 -IIA

“…Guidelines of the Canadian Council on Animal Care were followed for all our studies in a protocol approved by the Animal Welfare Committee at Laval University. Eight-week-old male C57BL/6J (sPLA 2 -IIA −/− ), transgenic human sPLA 2 -IIA (sPLA 2 -IIA TGN ) (28,44), and ALOX12 −/− (71) mice backcrossed 10 times in a C57BL/6J background were obtained from The Jackson Laboratory. sPLA 2 -IIA −/− ALOX12 −/− mice in a C57BL/6J background were crossed with sPLA 2 -IIA TGN ALOX12 +/+ mice in a C57BL/6J background (sPLA 2 -IIA TGN hemizygous).…”

“…Because C57Bl6/J mice naturally lack sPLA 2 -IIA (28), we used transgenic mice expressing human sPLA 2 -IIA (sPLA 2 -IIA TGN , in a C57Bl6/J background) (44) and included WT C57Bl6/J mice as controls. We observed that on injection into the tail vein, fluorescent ALOX12 +/+ MPs quickly localized inside neutrophils in the arthritic ankles of sPLA 2 -IIA-expressing mice (Fig.…”

“…Under the hypothesis that the internalization of MPs by neutrophils might be biologically relevant, we verified the impact of the concerted activities of sPLA 2 -IIA and 12-LO in vivo. To this end, we crossed ALOX12 −/− mice with sPLA 2 -IIA TGN mice, which reportedly exhibit skin abnormalities reminiscent of psoriasis but with no neutrophil infiltration (44), to generate sPLA 2 -IIA TGN ALOX12 −/− mice. We observed that ablation of the ALOX12 gene in sPLA 2 -IIA TGN mice had no effect on the skin phenotype, although 12-LO expression was eliminated in blood platelets (Fig.…”

Pseudomonas aeruginosa eradicates Staphylococcus aureus by manipulating the host immunity

“…****Po0.0001 determined by one-way analysis of variance followed by Bonferroni multiple's comparisons test. transgenic mice overexpressing human sPLA2-IIA (sPLA2-IIATg) 25 . Increased levels of sPLA2 activity were found in bronchoalveolar lavage fluids (BALFs) from these mice compared with their littermates c57BL/6, which are naturally deficient for sPLA2-IIA (sPLA2-IIA-Wt) 25 ( Supplementary Fig.…”

“…We next examined whether endogenously produced sPLA2-IIA exerts a role in SA clearance in airways. Given that mice naturally exhibit very low sPLA2-IIA expression in the lungs 25,26 , we used guinea pigs as animal model known to produce high pulmonary levels of sPLA2-IIA (refs 17,27). At first, we examined the effect of PA and SA (5 Â 10 6 c.f.u.…”