Bombesin (Bn) and related agonists produce a potent contractile response in guinea pig peripheral airways in vitro, with the following relative potencies: bombesin > gastrin-releasing peptide (GRP) > neuromedin C >> neuromedin B. Specific GRP-preferring receptor antagonists, namely [D-Phe6]Bn-(6-13)methyl ester and [D-Phe6,Cpa14,psi 13-14]Bn(6-14)-NH2, inhibited bombesin-induced lung contraction with high potencies [negative logarithm of the molar concentration of antagonist that produces a twofold shift to the right in the agonist dose-response curve (pA2) of 7.1 and 7.2, respectively], whereas the less-specific antagonist [Leu14,psi 13-14]Bn has a lower one (pA2 of 5.6). In binding studies, the high affinities of GRP, [D-Phe6]Bn(6-13)methyl ester and [D-Phe6,Cpa14,psi 13-14]Bn(6-14)NH2 in contrast with the low affinity of neuromedin B agree with the hypothesis that GRP-preferring receptors are involved in bombesin-induced bronchoconstriction. Bombesin-induced bronchoconstriction is unaffected by atropine, hexamethonium, propranolol, triprolidine, methysergide, Ro 19-3704, and indomethacin or AA-861, suggesting that the Bn response does not occur via a mechanism involving the corresponding endogeneous agents or via the release of arachidonic acid metabolites. Moreover, the effect of Bn is insensitive to capsaicin pretreatment, excluding the involvement of endogeneous neuropeptides. Present results provide evidence that Bn-induced bronchoconstriction results from a direct effect of Bn on bronchial smooth muscle GRP-preferring receptors.

Objective. To investigate synovial fluid (SF) for the presence of CR1 and to study its relationship to SF leukocytes and to serum levels of soluble CR1 (sCR1) in patients with rheumatic diseases.Methods. Synovial fluids were collected from 35 patients with rheumatoid arthritis (RA) and 26 patients with other inflammatory joint diseases. Total CR1 in the SF and serum were measured with a sandwich enzymelinked immunosorbent assay (ELISA) that recognized both soluble and transmembrane forms of CR1. The characteristics of CR1 in SF were analyzed by ultracentrifugation and by a second ELISA specific for transmembrane CR1.Results. CR1 was found in all SF samples tested (range 5-281 ng/ml). SF CR1 was higher in patients with RA (mean f SD 81 -C 66 ng/ml) than in those with other inflammatory joint diseases (31.8 & 23.8 ng/ml) (P < 0.001). Serum sCRl was not significantly increased in the patients compared with the normal subjects. There was no correlation between serum sCRl and SF CR1. In 44% of the patients, the SF CR1 level was higher than the serum sCRl level. A fraction (3040%) of SF CR1 was pelleted by ultracentrifugation and, unlike serum sCR1, it reacted in an ELISA specific for transmembrane CR1. Thus, SF contained 2 forms of CRl: a membrane-associated and a soluble form, which was confirmed by sucrose density-gradient ultracentrifugation. SF CR1 levels correlated directly with the number of SF total leukocytes and polymorphonuclear

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Complement receptor type 1 is expressed by erythrocytes and most leukocytes. A soluble form is shed from the leukocytes and found in plasma (sCR1). sCR1 is a powerful inhibitor of complement. We report an increased sCR1 in the plasma of leukemia patients, up to levels producing measurable complement inhibition. Half of the 180 patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL) had sCR1 levels above the normal range. The highest levels were observed in T-ALL (17 patients). The complement function of a T-ALL serum was improved by blocking sCR1 with a specific mAb (3D9). Measurements in 16 peripheral stem cell donors before and after granulocyte colony-stimulating factor (G-CSF) administration showed an increase in sCR1 (before, 43.8 ؎ 15.4; at day 5, 118.3 ؎ 44.7 ng/mL; P F 0.0001). This increase paralleled the increase in total leukocyte counts and was concomitant with de novo leukocyte mRNA CR1 expression in all three individuals tested. Whether pharmacological intervention may be used to up-regulate sCR1 so as to inhibit complement in vivo should be further investigated. J. Leukoc. Biol. 65: 94-101; 1999.

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