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Platelets play important roles in the late phase of the immediate hypersensitivity reaction  Risa Tamagawa-Mineoka, MD, PhD, Norito Katoh, MD, PhD, Saburo.

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Presentation on theme: "Platelets play important roles in the late phase of the immediate hypersensitivity reaction  Risa Tamagawa-Mineoka, MD, PhD, Norito Katoh, MD, PhD, Saburo."— Presentation transcript:

1 Platelets play important roles in the late phase of the immediate hypersensitivity reaction 
Risa Tamagawa-Mineoka, MD, PhD, Norito Katoh, MD, PhD, Saburo Kishimoto, MD, PhD  Journal of Allergy and Clinical Immunology  Volume 123, Issue 3, Pages e9 (March 2009) DOI: /j.jaci Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 Changes in ear swelling responses after ovalbumin (OVA) challenge. Ear thickness was measured in the ears of mice (6 per group) after administration of APAS or CS (A), or busulfan or vehicle (B). The ear weight was examined 1 hour (C) and 24 hours (D) after challenge. ∗∗P < .01 vs CS or vehicle administration in OVA-challenged mice. NS, Not significant. Journal of Allergy and Clinical Immunology  , e9DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 Histologic examination of ear skin. Skin tissue was excised 1 hour (A-D) and 24 hours (E-H) after ovalbumin challenge. A and E, Injection of vehicle alone with CS administration. B and F, Injection of ovalbumin with CS administration. C and G, Injection of vehicle alone with APAS administration. D and H, Injection of ovalbumin with APAS administration. Hematoxylin and eosin. Original magnification ×200. Bar = 50 μm. Journal of Allergy and Clinical Immunology  , e9DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 Effect of platelet restoration on ear swelling responses and leukocyte infiltration. Mice (6 per group) were injected intravenously with platelet suspension or vehicle. Ear swelling responses (A) and the number of infiltrated cells (B) were examined. Data are shown as percentages of the basal number of cells in the dermis 24 hours after challenge ∗∗P < .01 vs mice injected with vehicle. OVA, Ovalbumin. Journal of Allergy and Clinical Immunology  , e9DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 Necessity of platelet P-selectin for cutaneous leukocyte recruitment. P-selectin expression on platelets (A) and the number of platelet-leukocyte complexes (B) were examined. Platelets isolated from P-selectin knockout (P-selectin–/–) mice (C) or treated with anti–P-selectin antibody (D) were injected. Data are shown as percentages of basal values in sham-sensitized mice or in mice injected with vehicle (5 mice per group). ∗P < .05; ∗∗P < .01. OVA, Ovalbumin; WT, wild-type. Journal of Allergy and Clinical Immunology  , e9DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 Effect of platelet-derived soluble factors on leukocyte recruitment into skin. Washed platelets were stimulated with TRAP. The activated platelet supernatant was injected into ear skin of APAS-treated mice (5 per group) just before challenge, after adding anti–MIP-1α, anti-RANTES, anti-TARC, or isotype control antibody to the supernatant. The supernatant of platelets fixed without stimulation with TRAP served as a control. ∗∗P < .01. Journal of Allergy and Clinical Immunology  , e9DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig 6 Effect of antiplatelet drugs on ear swelling responses and leukocyte infiltration. The ear weight was examined 1 hour (A) and 24 hours (B) after challenge, and skin tissue was examined 24 hours after challenge (C; 5 mice per group). Data are shown as the percentage of the basal number of cells in the dermis after vehicle administration. ∗∗P < .01. NS, Not significant. Journal of Allergy and Clinical Immunology  , e9DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

8 Changes in ear swelling responses after ovalbumin (OVA) challenge
Changes in ear swelling responses after ovalbumin (OVA) challenge. The ear weight of W/Wv mice (A) and that of mice injected with APAS (C) or challenged (E) repeatedly and the ear thickness of mice injected with neuraminidase (B) were examined. The myeloperoxidase (MPO) and eosinophil peroxidase activities of the skin tissue were measured (D). Six mice per group. ∗∗P < .01 vs vehicle administration in OVA-challenged mice. Journal of Allergy and Clinical Immunology  , e9DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

9 Effect of platelet addition on ear swelling responses and chemokine release from in vitro ovalbumin-challenged platelets. The ear weight of mice without platelet depletion (6 per group) was examined after injection of platelet suspension (A). The levels of MIP-1α, RANTES, and TARC were measured in triplicate in the supernatant of platelets treated with serum of sensitized mice and ovalbumin (B). ∗P < .05. NS, Not significant. Journal of Allergy and Clinical Immunology  , e9DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

10 Effect of platelet restoration on formation of platelet-leukocyte complexes. Mice (5 per group) were injected with platelet suspension obtained from ovalbumin (OVA)-sensitized or sham-sensitized mice, or P-selectin–deficient mice. The number of platelet-leukocyte complexes in blood was examined. Data are shown as percentages of basal values in sham-sensitized mice (A). Chemokine levels were measured in triplicate in the supernatant of P-selectin–deficient platelets (B). ∗P < .05; ∗∗P < .01. WT, Wild-type. NS, Not significant. Journal of Allergy and Clinical Immunology  , e9DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

11 Effect of platelet-derived soluble factors on leukocyte recruitment into skin. The activated platelet supernatant was injected into ear skin of mice with (A) and without (B) platelet depletion, without challenge. Vehicle treated with antichemokine antibodies was also injected into ear skin (C). Data are shown as percentages of basal numbers in mice injected with the supernatant of fixed platelets. Five mice per group. ∗∗P < .01. NS, Not significant. Journal of Allergy and Clinical Immunology  , e9DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

12 Effect of antiplatelet drugs on formation of platelet-leukocyte complexes and chemokine release from platelets. P-selectin expression on platelets and the number of platelet-leukocyte complexes were examined in the blood of mice (6 per group) treated with antiplatelet agents (A). Chemokine levels were measured in triplicate in the supernatant of platelets treated with antiplatelet agents (B). ∗∗P < .01. OVA, Ovalbumin. Journal of Allergy and Clinical Immunology  , e9DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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