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Early administration of serelaxin was associated with a reduction of 180-day mortality, and this occurred with fewer signs of organ damage and more rapid relief of congestion during the first days after admission.

In

GROa and neutrophil-activating peptide 2 (NAP-2), like their analog interleukin 8 , are considered to be inflammatory mediators since they recruit and activate neutrophil leukocytes. After introduction of tyrosines by substitution for other residues at the C terminus, GROa and NAP-2 were labeled with 125I and used for binding studies. A total of 60,000-90,000 receptors per neutrophil were found for either ligand. Of these 30-45% were of high affinity with a mean Kd value of 0.3 and 0.7 nM for GROa and NAP-2, respectively, and 55-70% of low affinity (Kd = 30 nM). Two proteins of "70 kDa and 44 kDa (p70 and p44) were specifially cross-linked with labeled GROa, NAP-2, and IL-8. Unlabeled IL-8 fully inhibited this crossing and the binding oflabeled Among the growing number of interleukin 8 (IL-8)-related chemotactic cytokines, neutrophil-activating peptide 2 (NAP-2) and GROa were studied extensively because oftheir possible involvement in the pathophysiology of inflammation (1-4) and tumor growth (5, 6). Responses with neutrophils, the principal target cells for all three cytokines, include chemotaxis, shape change, mobilization of cytosolic free calcium, release of granule components, upregulation of adhesion receptors, and the respiratory burst (7-12). Several recent reports have described receptors for IL-8 on human neutrophils (13)(14)(15)(16)(17). With one exception (13), these studies show that IL-8 binds to a single class of high-affinity receptors (Kd = 0.2-4 nM) with densities reported to be between 20,000 and 75,000 sites per cell. Cross-linking experiments revealed either one (14) or two (15, 17) receptor proteins with molecular masses ranging from 44 to 78 kDa. Recently, cDNAs for two IL-8 receptors with seven putative transmembrane domains typical of guanine nucleotide binding protein (G protein)-coupled receptors have been described (18, 19).Studies of the biochemical and binding properties of receptors for GROa and NAP-2 were hampered by the absence of tyrosines suitable for radioiodination. By substitution of residues at or close to the C terminus with tyrosines, we have obtained analogs with similar biological activities as the natural peptides that could be labeled to high-specific activities with 1251. Using these analogs, we were able to identify GROa and NAP-2 receptors on human neutrophils by direct binding assays and to compare them with the receptors for IL-8. The results of the present paper demonstrate the existence of two distinct receptors on human neutrophils that recognize GROa and NAP-2 as well as IL-8. MATERIALS AND METHODSMaterials. Aprotinin, chymostatin, leupeptin, bovine serum albumin, EDTA, PEG 6000, diisopropyl fluorophosphate, deoxycholate, Nonidet P40, polyethylenimine, and D-(+)-sucrose were obtained from Fluka; gelatin and phenylmethylsulfonyl fluoride were from Sigma; disuccinimidyl suberate was from Pierce; DNase I was from Boehringer Mannheim; 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) and dodecyl f3-maltoside were from Calbiochem-Behring; d...