Ulich T R, Keys M, Ni R X, del Castillo J, Dakay E B
Department of Pathology, University of California, Irvine Medical School 92717.
J Leukoc Biol. 1988 Jan;43(1):5-10. doi: 10.1002/jlb.43.1.5.
Stable prostaglandin analogs are known to induce lymphopenia and neutrophilia in a dose-dependent fashion after subcutaneous injection in rats. The purpose of the present investigation is to determine whether the prostaglandin-induced changes in circulating leukocytes might be secondary to hypotension with the ensuing release of adrenal hormones. The adrenal medullary catecholamine epinephrine was found to induce neutrophilia in both intact and adrenalectomized rats, and the glucocorticosteroid analog dexamethasone induced a profound lymphopenia in rats as reported by previous investigators. A stable analog of PGF2 alpha (15-S-15-methyl PGF2 alpha; M-PGF2 alpha) at the dose of 1 mg/kg induced marked systemic hypotension 1 h after injection, with lymphopenia and neutrophilia 6 h after injection. The non-prostanoid hypotensive agent captopril, at a dose of 63 mg/kg, induced a hypotension of similar magnitude and kinetics to that induced by prostaglandin. Captopril also induced lymphopenia and neutrophilia at 6 h, although the neutrophilia was of lesser magnitude than that induced by prostaglandins. The prostaglandin-induced lymphopenia was found to be mediated, at least in part, by the hypotension-induced release of adrenal hormones, as evidenced by the abrogation of lymphopenia in prostaglandin-treated adrenalectomized rats. Captopril-treated adrenalectomized rats, however, did develop a significant lymphopenia, suggesting that hypotension can result in lymphopenia even in adrenalectomized rats. The M-PGF2 alpha-induced neutrophilia in adrenalectomized rats, by comparison to captopril-induced neutrophilia in adrenalectomized rats, was greater than the neutrophilia expected as the result of hypotension alone. Indeed, the M-PGF2 alpha-induced neutrophilia in adrenalectomized rats was greater than the captopril-induced neutrophilia in sham-adrenalectomized rats. Thus, a portion of the neutrophilia induced by M-PGF2 alpha in intact rats may be mediated through adrenal-independent, hemodynamic-independent mechanisms. The possibility that M-PGF2 alpha might be inducing neutrophilia via an endotoxin-like stress reaction was investigated by examining changes in circulating white blood cells in intact and adrenalectomized C3H/HeN (endotoxin-sensitive) and C3H/HeJ (endotoxin-resistant) mice after prostaglandin administration. No quantitative differences in the prostaglandin-induced neutrophilia were noted in C3H/HeJ mice as compared to the C3H/HeN mice.(ABSTRACT TRUNCATED AT 400 WORDS)
已知稳定的前列腺素类似物在大鼠皮下注射后会以剂量依赖的方式诱导淋巴细胞减少和中性粒细胞增多。本研究的目的是确定前列腺素诱导的循环白细胞变化是否可能继发于低血压以及随之而来的肾上腺激素释放。发现肾上腺髓质儿茶酚胺肾上腺素在完整大鼠和肾上腺切除大鼠中均能诱导中性粒细胞增多，并且糖皮质激素类似物地塞米松如先前研究者所报道的那样在大鼠中诱导了严重的淋巴细胞减少。剂量为1mg/kg的PGF2α稳定类似物（15-S-15-甲基PGF2α；M-PGF2α）在注射后1小时引起明显的全身低血压，在注射后6小时引起淋巴细胞减少和中性粒细胞增多。剂量为63mg/kg的非前列腺素类降压药卡托普利诱导的低血压在幅度和动力学上与前列腺素诱导的相似。卡托普利在6小时时也诱导了淋巴细胞减少和中性粒细胞增多，尽管中性粒细胞增多的幅度小于前列腺素诱导的。发现前列腺素诱导的淋巴细胞减少至少部分是由低血压诱导的肾上腺激素释放介导的，这在前列腺素处理的肾上腺切除大鼠中淋巴细胞减少的消除中得到了证明。然而，卡托普利处理的肾上腺切除大鼠确实出现了明显的淋巴细胞减少，这表明低血压即使在肾上腺切除大鼠中也可导致淋巴细胞减少。与卡托普利在肾上腺切除大鼠中诱导的中性粒细胞增多相比，M-PGF2α在肾上腺切除大鼠中诱导的中性粒细胞增多大于仅由低血压预期的中性粒细胞增多。实际上，M-PGF2α在肾上腺切除大鼠中诱导的中性粒细胞增多大于卡托普利在假肾上腺切除大鼠中诱导的中性粒细胞增多。因此，M-PGF2α在完整大鼠中诱导的部分中性粒细胞增多可能通过不依赖肾上腺、不依赖血流动力学的机制介导。通过检查前列腺素给药后完整和肾上腺切除的C3H/HeN（对内毒素敏感）和C3H/HeJ（对内毒素有抗性）小鼠循环白细胞的变化，研究了M-PGF2α是否可能通过类似内毒素的应激反应诱导中性粒细胞增多的可能性。与C3H/HeN小鼠相比，在C3H/HeJ小鼠中未观察到前列腺素诱导的中性粒细胞增多的定量差异。（摘要截短至400字）
