Dix Randy, Orth Teresa, Allen Julie, Wood John G, Gonzalez Norberto C
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
J Appl Physiol (1985). 2003 Dec;95(6):2495-502. doi: 10.1152/japplphysiol.00735.2003. Epub 2003 Aug 29.
Systemic hypoxia, produced by lowering inspired Po2, induces a rapid inflammation in several microcirculations, including cremaster muscle. Mast cell activation is a necessary element of this response. Selective reduction of cremaster microvascular Po2 (PmO2) with normal systemic arterial Po2 (PaO2; cremaster hypoxia/systemic normoxia), however, does not elicit increased leukocyte-endothelial adherence (LEA) in cremaster venules. This could be due to a short time of leukocyte exposure to the hypoxic cremaster environment. Conversely, LEA increases when PaO2 is lowered, while cremaster PmO2 remains high (cremaster normoxia/systemic hypoxia). An alternative explanation of these results is that a mediator released from a central site during systemic hypoxia initiates the inflammatory cascade. We hypothesized that if this is the case, cremaster mast cells would be activated during cremaster normoxia/systemic hypoxia, but not during cremaster hypoxia/systemic normoxia. The microcirculation of rat cremaster muscles was visualized by using intravital microscopy. Cremaster PmO2 was measured with a phosphorescence quenching method. Cremaster hypoxia/systemic normoxia (PmO2 7 +/- 1 Torr, PaO2 87 +/- 2 Torr) did not increase LEA; however, topical application of the mast cell activator compound 48/80 under these conditions did increase LEA. The effect of compound 48/80 on LEA was blocked by topical cromolyn, a mast cell stabilizer. LEA increased during cremaster normoxia/systemic hypoxia, (PmO2 64 +/- 5 Torr, PaO2 33 +/- 2 Torr); this increase was blocked by topical cromolyn. The results suggest that mast cell stimulation occurs only when PaO2 is reduced, independent of cremaster PmO2, and support the idea of a mediator that is released during systemic hypoxia and initiates the inflammatory cascade.
通过降低吸入氧分压产生的全身性低氧会在包括提睾肌在内的多个微循环中引发快速炎症反应。肥大细胞活化是这种反应的必要组成部分。然而，在全身动脉氧分压（PaO2）正常的情况下选择性降低提睾肌微血管氧分压（PmO2；提睾肌低氧/全身正常氧分压），并不会导致提睾肌微静脉中白细胞-内皮细胞黏附（LEA）增加。这可能是由于白细胞暴露于低氧提睾肌环境的时间较短。相反，当PaO2降低而提睾肌PmO2保持较高水平时（提睾肌正常氧分压/全身低氧），LEA会增加。对这些结果的另一种解释是，全身性低氧期间从中心部位释放的一种介质启动了炎症级联反应。我们假设，如果是这种情况，在提睾肌正常氧分压/全身低氧期间提睾肌肥大细胞会被激活，但在提睾肌低氧/全身正常氧分压期间则不会。通过活体显微镜观察大鼠提睾肌的微循环。用磷光猝灭法测量提睾肌PmO2。提睾肌低氧/全身正常氧分压（PmO2 7±1托，PaO2 87±2托）不会增加LEA；然而，在这些条件下局部应用肥大细胞激活剂化合物48/80确实会增加LEA。化合物48/80对LEA的作用被肥大细胞稳定剂局部应用的色甘酸阻断。在提睾肌正常氧分压/全身低氧期间（PmO2 64±5托，PaO2 33±2托）LEA增加；这种增加被局部应用的色甘酸阻断。结果表明，肥大细胞刺激仅在PaO2降低时发生，与提睾肌PmO2无关，并支持了全身性低氧期间释放一种介质并启动炎症级联反应的观点。
