Mast cell activation by fibrinogen-related homologous c-terminal peptides (haptides) modulates systemic blood pressure Maamoun Basheer, MSc, Herzl Schwalb,

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Presentation transcript:

Mast cell activation by fibrinogen-related homologous c-terminal peptides (haptides) modulates systemic blood pressure Maamoun Basheer, MSc, Herzl Schwalb, PhD, Maoz Nesher, MSc, Dan Gilon, MD, Irit Shefler, PhD, Yoseph A. Mekori, MD, Oz M. Shapira, MD, Raphael Gorodetsky, PhD Journal of Allergy and Clinical Immunology Volume 126, Issue 5, Pages 1041-1048 (November 2010) DOI: 10.1016/j.jaci.2010.07.020 Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Effect of escalating doses of intravenous (IV) administration of haptides on blood-pressure and heart rate in the rat. A, An arterial pressure records at baseline and 6 minutes after intravenous injection of 1.5 mg/kg Cβ showing a triphasic response effect on blood pressure (lines 1-3). Haptides effect (35-560 μg/kg) on diastolic, systolic, and mean arterial BP as well as heart rate were tested (n = 6) (B-E, respectively). Results were compared with the control peptide Cα (∗P < .05; ∗∗P < .01). Journal of Allergy and Clinical Immunology 2010 126, 1041-1048DOI: (10.1016/j.jaci.2010.07.020) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Effect of haptides versus scrambled haptides sequences on DBP, SBP, and MAP.Rats were injected with 280 μg/kg of the haptides Cβ, preCγ or their scrambled versions as well as with whole human fibrinogen (n = 6). The results (mean ± SE) are presented as percentages of the baseline values. The effects are compared with the baseline values (P < .01). Journal of Allergy and Clinical Immunology 2010 126, 1041-1048DOI: (10.1016/j.jaci.2010.07.020) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Compound 48/80–mast cell activator and serotonin decreases rat BP in the same manner as haptides. A, Trace record of arterial pressure at baseline and following intravenous (IV) injection in rat of 2 mg/kg compound 48/80. Hemodynamic parameters in response to escalating doses of compound 48/80 and serotonin are summarized in B and C, respectively (n = 6). Results presented as percentages of the baseline (mean ± SE). The effects are compared with the baseline values (∗P < .05; ∗∗P < .01). Journal of Allergy and Clinical Immunology 2010 126, 1041-1048DOI: (10.1016/j.jaci.2010.07.020) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Histaminergic blockade attenuates haptides' effect on rat blood pressure. A, Effect of haptides (280 μg/kg) on hemodynamic parameters in rats pretreated with cromolyn or with pyrilamine and cimetidine. B, A chart of blood pressure drop caused by intravenous haptide administration and pretreatment with cromolyn. C, Effects of haptides on BP in rats pretreated with fexofenadine or famotidine. The results (mean ± SE) are presented as percentages of the baseline (n = 6; ∗P < .05). Journal of Allergy and Clinical Immunology 2010 126, 1041-1048DOI: (10.1016/j.jaci.2010.07.020) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Haptides activate rat mast cells. Effect of haptides on histamine release in isolated rat peritoneal mast cells. The mast cells (2 × 105 cells/mL) were preincubated for 30 minutes with 100 μg/mL haptides (A). Plasma histamine level in rats pretreated with 280 μg/kg preCγ, Cβ, or the control (Cα; n = 5; B). Results are presented as means ± SEs. The effects are compared with the control peptide Cα values (∗P < .01). Journal of Allergy and Clinical Immunology 2010 126, 1041-1048DOI: (10.1016/j.jaci.2010.07.020) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 6 Effect of haptides on degranulation of cultured LAD2 cells. Haptides effects on LAD2 cells activation as monitored by β-hex secretion. A, Dose response of 2-minute incubation with haptides. The cells were preincubated for 2 minutes (B) or 30 minutes (C) with 50 or 100 μg/mL with haptides preCγ, Cβ, or the control Cα (n = 4). Values are percentages of total β-hex release. The haptides effects are presented relative to Cα (∗∗P < .01). Journal of Allergy and Clinical Immunology 2010 126, 1041-1048DOI: (10.1016/j.jaci.2010.07.020) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 7 Effect of intravenous administration of ketanserin, 5-HT2 receptor antagonists, on BP variability in rats. Trace records of arterial BP at baseline and 6 minutes after injection into the femoral veins of 2 mg/kg haptides Cβ (A) or preCγ (C). Tracings of arterial BP records where both haptides were injected 10 minutes after a single dose of intravenous ketanserin (1 mg/kg) administration are presented in B and D, respectively. Journal of Allergy and Clinical Immunology 2010 126, 1041-1048DOI: (10.1016/j.jaci.2010.07.020) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions