Macari D M, Teixeira M M, Hellewell P G
Department of Applied Pharmacology, Imperial College of Science, Technology & Medicine, London, United Kingdom.
J Immunol. 1996 Aug 15;157(4):1684-92.
Eosinophils are important inflammatory cells in allergic diseases. Recent evidence suggests that priming mechanisms in the blood may be important for effective eosinophil recruitment to sites of allergic inflammation. We have investigated whether priming an inflammatory site could enhance eosinophil recruitment in vivo. Pretreatment of skin sites in the guinea pig with a low dose (30 ng) of LPS, which had little effect on eosinophil accumulation alone, enhanced by up to threefold the 111In-eosinophil accumulation in response to a passive cutaneous anaphylactic reaction and to intradermally injected eosinophil chemoattractants (leukotriene B4, PAF, and C5ades Arg). In contrast, LPS pretreatment did not enhance accumulation of 111In-neutrophils. Priming was seen only with a 1-h pretreatment time and was not associated with an increase in local edema or a change in cutaneous blood flow. It was independent of local protein synthesis, as assessed using cycloheximide, and was unaffected by a PAF antagonist, a 5-lipoxygenase inhibitor, and the IL-1 receptor antagonist. The priming response was, however, reduced by co-injection with the LPS of TNFR-IgG, but not of CD4-IgG. Blockade of CD18 showed this adhesion molecule to be critical for eosinophil accumulation, and LPS-primed sites were inhibited as effectively as nonprimed sites. In conclusion, low dose LPS pretreatment of guinea pig skin sites primes for eosinophil accumulation induced by intradermally injected inflammatory mediators and cutaneous anaphylactic reaction. This may be an important process by which eosinophil recruitment is modulated in vivo.
嗜酸性粒细胞是过敏性疾病中的重要炎症细胞。最近的证据表明，血液中的致敏机制对于嗜酸性粒细胞有效募集至过敏性炎症部位可能很重要。我们研究了对炎症部位进行致敏是否能增强体内嗜酸性粒细胞的募集。用低剂量（30 ng）的脂多糖（LPS）预处理豚鼠的皮肤部位，单独使用时对嗜酸性粒细胞的积聚影响很小，但在被动皮肤过敏反应和皮内注射嗜酸性粒细胞趋化因子（白三烯B4、血小板活化因子和C5a去精氨酸）时，可使铟 - 111标记的嗜酸性粒细胞积聚增加多达三倍。相比之下，LPS预处理并未增强铟 - 111标记的中性粒细胞的积聚。仅在预处理1小时时观察到致敏现象，且与局部水肿增加或皮肤血流变化无关。如用放线菌酮评估，其与局部蛋白质合成无关，且不受血小板活化因子拮抗剂、5 - 脂氧合酶抑制剂和白细胞介素 - 1受体拮抗剂的影响。然而，与肿瘤坏死因子受体 - IgG的LPS共同注射可降低致敏反应，但与CD4 - IgG共同注射则无此作用。阻断CD18表明该黏附分子对嗜酸性粒细胞积聚至关重要，LPS致敏部位与未致敏部位一样有效地受到抑制。总之，低剂量LPS预处理豚鼠皮肤部位可使皮内注射炎症介质和皮肤过敏反应诱导的嗜酸性粒细胞积聚致敏。这可能是体内调节嗜酸性粒细胞募集的一个重要过程。
