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Transplantation of corneal epithelial stem cells can restore useful vision in some patients with severe ocular-surface disorders.

Conclusions regarding the contribution of low molecular weight secretory phospholipase A 2 (sPLA 2 ) enzymes in eicosanoid generation have relied on data obtained from transfected cells or the use of inhibitors that fail to discriminate between individual members of the large family of mammalian sPLA 2 enzymes. To elucidate the role of group V sPLA 2 , we used targeted gene disruption to generate mice lacking this enzyme. Zymosan-induced generation of leukotriene C 4 and prostaglandin E 2 was attenuated ϳ50% in peritoneal macrophages from group V sPLA 2 -null mice compared with macrophages from wild-type littermates. Furthermore, the early phase of plasma exudation in response to intraperitoneal injection of zymosan and the accompanying in vivo generation of cysteinyl leukotrienes were markedly attenuated in group V sPLA 2 -null mice compared with wild-type controls. These data provide clear evidence of a role for group V sPLA 2 in regulating eicosanoid generation in response to an acute innate stimulus of the immune response both in vitro and in vivo, suggesting a role for this enzyme in innate immunity.The first step in the biosynthesis of eicosanoids is the release of arachidonic acid from cell membrane phospholipids by phospholipase A 2 . Several classes of phospholipase A 2 have been described in mammals (1, 2). Cytosolic phospholipase A 2 (cPLA 2 ) 1 ␣ is an 85-kDa cytosolic enzyme that uses a catalytic serine residue and preferentially cleaves arachidonic acid from cell membrane phospholipids (3). The Ca 2ϩ -dependent translocation of cPLA 2 -␣ from the cytosol to the nuclear envelope (4), a prominent site of eicosanoid biosynthesis, is dependent on a Ca 2ϩ -dependent lipid binding (C-2) domain. Paralogues of cPLA 2 -␣ (cPLA 2 -␤ and cPLA 2 -␥) have been described previously (5, 6). cPLA 2 -␤ has a M r of 110,000 and shares 30% identity with cPLA 2 -␣, including a functional C-2 domain. cPLA 2 -␥ has a M r of 61,000, shares 29% sequence identity with cPLA 2 -␣, lacks a C-2 domain, and is Ca 2ϩ -independent. Mammalian low molecular weight secretory phospholipase A 2 (sPLA 2 ) enzymes, which are now 10 in number, are characterized by a conserved motif containing a catalytic histidine residue, by their relatively small size of ϳ14 kDa, and by their highly disulfide-linked tertiary structures (7-13). They are distinguished from one another by their structures, their biochemical properties, and their tissue distribution. Calcium-independent phospholipase A 2 enzymes have been described in myocardium and in leukocytes (14, 15). They have been implicated in membrane remodeling, regulation of store operated calcium channels, apoptosis, and release of arachidonic acid. The fourth group of phospholipase A 2 enzymes comprises the acetyl hydrolases of platelet activating factor (16).Given the complexity and size of the phospholipase A 2 family, targeted gene disruption is a suitable approach to elucidating the role(s) of individual enzymes and proved fruitful in determining the role of cPLA 2 -␣ in regulating eicosan...

Increase of the oxidative stress status in the conjunctiva of SS patients appears to have a role in the pathogenesis of dry eye disease. A close relationship may exist between reactive oxygen species (ROS) production, lipid peroxidation related membrane damage, and inflammatory processes in dry eye.