Allen P Kaplan

High molecular weight kininogen (HK) and factor XII are known to bind to human umbilical vein endothelial cells (HUVEC) in a zinc-dependent and saturable manner indicating that HUVEC express specific binding site(s) for those proteins. However, identification and immunochemical characterization of the putative receptor site(s) has not been previously accomplished. In this report, we have identified a cell surface glycoprotein that is a likely candidate for the HK binding site on HUVECs. ...

Fletcher factor-deficient plasma is deficient in prekallikrein and therefore generates no bradykinin upon activation with kaolin. It also possesses a diminished rate of kaolin-activable coagulation and fibrinolysis and possesses a defect in kaolin-activable chemotactic activity. These abnormalities are also corrected by reconstitution with purified prekallikrein. Addition of intact activated Hageman factor corrected the coagulation, fibrinolytic, and chemotactic defects and addition of ...

BACKGROUND: Proof-of-concept studies with omalizumab in patients with chronic idiopathic urticaria (CIU) have shown significant decreases in mean urticaria activity scores (UASs).

OBJECTIVE: We sought to evaluate the efficacy and safety of omalizumab in patients with CIU who remain symptomatic despite concomitant H(1)-antihistamine therapy.

METHODS: This phase II, prospective, double-blind, placebo-controlled, dose-ranging study investigated omalizumab in patients aged 12 to 75 years in ...

The activation and function of surface-bound Hageman factor in human plasma are dependent upon both high molecular weight (HMW) kininogen and prekallikrein. HMW kininogen does not affect the binding of Hageman factor to surfaces, but it enhances the function of surface-bound Hageman factor as assessed by its ability to activate prekallikrein and Factor XI. The initial conversion of prekallikrein to kallikrein by the surface-bound Hageman factor in the presence of HMW kininogen is ...

BACKGROUND: Few data are available that describe response patterns in patients with chronic idiopathic urticaria (CIU)/chronic spontaneous urticaria (CSU) treated with omalizumab.

OBJECTIVE: We sought to describe response patterns by using data from the 3 pivotal omalizumab CIU/CSU trials.

METHODS: Every 4 weeks, randomized patients received dosing with placebo or 75, 150, or 300 mg of omalizumab (ASTERIA I: n = 318, 24 weeks; ASTERIA II: n = 322, 12 weeks) or placebo or 300 mg of ...

Although proteins of the kinin-forming pathway are bound along the surface of endothelial cells, the mechanism of activation of this proteolytic cascade is unclear. Endothelial cell surface proteins, gC1qR and cytokeratin 1, are capable of binding Factor XII and high molecular weight kininogen (HK) in a zinc-dependent reaction thus we considered the possibility that these proteins might catalyze initiation of the cascade. Incubation of Factor XII, prekallikrein, and HK with gC1qR or ...

Factor XII (FXII, plasma concentration 375 nM) is a critical member of the plasma contact activation system and is the zymogen form of FXIIa, a serine protease involved in intrinsic coagulation, complement activation, activation of factor VII, and generation of the vasoactive peptide bradykinin. As such its interaction with cells involved in inflammatory pathways can be of physiologic and pathologic significance. We have studied the binding of FXII to cultured human umbilical vein ...

BACKGROUND: Histamine release in chronic urticaria is initiated by cross-linking of the alpha subunit of FcepsilonRI by means of IgG antibody, followed by complement activation.

OBJECTIVE: We sought to further elucidate the mechanism by which complement augments histamine release and to assess the role of C5a.

METHODS: We first quantitated the ability of purified C5a to initiate basophil histamine release and to be inhibited by antibody directed to the C5a receptor. Using this antibody, ...

BACKGROUND: Previous studies have demonstrated infiltration of eosinophils, neutrophils, monocytes, and T cells in the skin of patients with chronic idiopathic urticaria (CIU), suggesting a possible T(H)2-type cytokine pathology analogous to the allergen-induced skin late-phase reaction (LPR).

OBJECTIVE: We sought to compare skin biopsy specimens from patients with CIU and the allergen-induced skin LPR for mRNA(+) cells for IL-4, IL-5, and IFN-gamma and inflammatory cell ...

Bradykinin is a major mediator of swelling in C1 inhibitor deficiency as well as the angioedema seen with ACE inhibitors and may contribute to bronchial hyperreactivity in asthma. Formation of bradykinin occurs in the fluid phase and along cell surfaces requiring interaction of factor XII, prekallikrein, and high M(r) kininogen (HK). Recent data suggest that activation of the kinin-forming cascade can occur on the surface of endothelial cells, even in the absence of factor XII. We sought ...

Plasma prorenin is an inactive form of renin (EC 3.4.99.19) that can be converted to active renin in acid-treated plasma by an endogenous serine protease that is active at alkaline pH (alkaline phase activation). To identify this enzyme we first tested the ability of Hageman factor fragments, plasma kallikrein (EC 3.4.21.8), and plasmin (EC 3.4.21.7) to activate prorenin in acid-treated plasma. All three enzymes initiated prorenin activation; 50% activation was achieved with Hageman ...

HMW-kininogen binds prekallikrein and factor XI to form two bimolecular complexes in plasma; upon addition of certain negatively charged surfaces, it functions as a coagulation cofactor and facilitates the activation of Hageman factor, prekallikrein and factor XI. We have investigated the mechanism by which HMW-kininogen functions in each of these steps. HMW-kininogen was found to augment the binding of prekallikrein and factor XI to kaolin in a plasma system sùggesting that the ...

High molecular weight kininogen (HK) attaches to endothelial cells by separate sites on the heavy and light chains and requires 15-50 microM zinc. Previously identified binding proteins include gC1qR, cytokeratin 1, and the urokinase plasminogen activator receptor; however, their relative contributions to binding are not yet clarified. We have prepared affinity columns to which were coupled either cleaved HK or peptide LDCNAEVYVVPWEKKIYPTVNCQPLGM derived from heavy-chain domain 3. ...