Fluhr, JW; Behne, MJ; Brown, BE; Moskowitz, DG; Selden, C; Mao-Qiang, M; ... Feingold, KR; + view all Fluhr, JW; Behne, MJ; Brown, BE; Moskowitz, DG; Selden, C; Mao-Qiang, M; Mauro, TM; Elias, PM; Feingold, KR; - view fewer (2004) Stratum corneum acidification in neonatal skin: Secretory phospholipase A(2) and the sodium/hydrogen antiporter-1 acidify neonatal rat stratum corneum. J INVEST DERMATOL , 122 (2) 320 - 329. 10.1046/j.0022-202X.2003.22204.x.
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At birth, human stratum corneum (SC) displays a near-neutral surface pH, which declines over several days to weeks to months to an acidic pH, comparable to that of adults. Recent studies suggest that an acidic pH is required for normal permeability barrier homeostasis and SC integrity/cohesion. We assessed here the basis for postnatal acidification in the neonatal rat, where SC pH, as measured with a flat surface electrode, declines progressively from near-neutral levels (pH 6.63) on postnatal days 0 to 1 to adult levels (pH 5.9) or even below over the subsequent 7 to 8 d. The postnatal decline in SC pH was paralleled by a progressive activation of a pH-dependent hydrolytic enzyme, beta-glucocerebrosidase. Because SC acidification could not be linked to commonly implicated exogenous factors, such as bacterial colonization, or the deposition of sebaceous gland products. We next assessed whether changes in one or more of three endogenous mechanisms demonstrate postnatal activity changes that contribute to the progressive development of an acidic SC pH. Although the histidine-to-urocanic acid pathway has been implicated in acidification of the adult SC, surface pH is completely normal in histidase-deficient (his/his, Peruvian) mice, ruling out a requirement for this mechanism. In contrast, when sodium/hydrogen antiporter-1 (NHE1), which predominantly acidifies membrane domains at the stratum granulosum-SC interface, is inhibited, postnatal acidification of the SC is partially blocked. Likewise, SC secretory phospholipase A(2) (sPLA(2)) activity, measured with a fluorometric assay, is low at birth, but increases progressively (by 66%) over the first 5 d after birth, and inhibition of sPLA(2) between days 0 to 1 and days 5 to 6 delays postnatal SC acidification. Together, these results describe a neonatal model, in which the development of an acidic surface pH can be ascribed, in part, to progressive SC acidification by two endogenous mechanisms, namely, sPLA(2) and NHE1, which are known to be important for acidification of adult rodent SC. Conversely, the impaired acidification of neonatal SC, which has important functional and clinical consequences, can be explained by the relatively low activities of one or both of these mechanisms at birth.
|Title:||Stratum corneum acidification in neonatal skin: Secretory phospholipase A(2) and the sodium/hydrogen antiporter-1 acidify neonatal rat stratum corneum|
|Keywords:||neonatal rat, stratum corneum pH, barrier function, PERMEABILITY BARRIER HOMEOSTASIS, BETA-GLUCOCEREBROSIDASE ACTIVITY, UROCANIC ACID, CUTANEOUS BACTERIA, EPIDERMAL BARRIER, MURINE EPIDERMIS, ACTIVE-SITE, PH GRADIENT, FETAL-RAT, DIFFERENTIATION|
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