scholarly journals Activated Complement Component 3 (C3) Is Required for Ultraviolet Induction of Immunosuppression and Antigenic Tolerance

1998 ◽  
Vol 187 (7) ◽  
pp. 1133-1138 ◽  
Author(s):  
Craig Hammerberg ◽  
Santosh K. Katiyar ◽  
Michael C. Carroll ◽  
Kevin D. Cooper
Keyword(s):  
Normal Skin ◽  
Complement Component ◽  
Primary Immune Response ◽  
Contact Sensitivity ◽  
Exposed Skin ◽  
Class Ii Mhc ◽  
Primary Sensitization ◽  
Antigen Presenting ◽  
Complement Component 3

Complement component 3 (C3), a critical regulator of innate immunity, may also play a role in the regulation of cognate immunity, such as contact sensitivity responses. Because ultraviolet (UV) radiation also activates C3 in the skin, we determined whether the immunosuppressed state that results when a contact sensitizer is applied through UVB-exposed skin requires the presence and activation of C3. This question was addressed through the use of C3-deficient mice, blockade of C3 cleavage to C3b, and accelerated degradation of iC3b by soluble complement receptor 1 (sCR1). Both C3-modulated systems totally reversed the failure to induce a contact sensitivity response to dinitrofluorobenzene (DNFB) upon primary sensitization at the UV-exposed site, as well as immunologic tolerance to a second DNFB immunization through normal skin. Treatment with sCR1 reduced the infiltration of CD11b+ leukocytes into the epidermis and dermis of UV-irradiated skin but did not reverse the UV-induced depletion of epidermal class II MHC+CD11blo Langerhans cells. These data, taken together with previous results showing abrogation of locally induced UV immunosuppression by in vivo anti-CD11b treatment, suggest a novel mechanism by which ligation of the leukocyte β2 integrin, CD11b, by iC3b molecules formed from C3 activation in UV-exposed skin, modifies cutaneous CD11b+ cells such that skin antigen-presenting cells are unable to sensitize in a primary immune response, but actively induce antigenic tolerance.

Surgical and physical stress increases circulating blood dendritic cell counts independently of monocyte counts

Blood ◽  
2001 ◽  
Vol 98 (1) ◽  
pp. 140-145 ◽  
Author(s):  
Christopher S. K. Ho ◽  
Jose Alejandro López ◽  
Slavica Vuckovic ◽  
Christopher M. Pyke ◽  
Richard L. Hockey ◽  
...  
Keyword(s):  
The Body ◽  
Exercise Stress ◽  
Primary Immune Response ◽  
Cell Counts ◽  
Elective Laparoscopic Cholecystectomy ◽  
And Function ◽  
Antigen Presenting ◽  
Blood Dendritic Cell ◽  
Unique Ability

Dendritic cells (DCs) are specialized antigen-presenting cells that have the unique ability to initiate a primary immune response. The effect of physiologic stress on circulating blood DCs has thus far not been studied. In this study, we applied a recently developed method of counting blood DCs to test the hypothesis that significant stress to the body such as surgery and exercise might induce measurable changes in the DC numbers, subsets, phenotype, and function. Twenty-six patients scheduled for elective laparoscopic cholecystectomy, 4 for elective hysterectomy, 56 controls, and 5 volunteers who underwent a stress exercise test were enrolled in the study. Absolute DC counts increased acutely (71.7% ± 11% [SEM],P = .0001) in response to the stress of surgery and dropped below preoperative levels (−25% ± 14% [SEM],P = .05) on days 2-3. The perioperative DC subset balance remained constant. Interestingly, DC counts changed independently of monocyte counts. Exercise also induced a rise in DC counts but coincidentally with monocyte counts. Surprisingly, no phenotypic or functional activation of DCs was seen in either stress situations in vivo. DCs are rapidly mobilized into the circulation in response to surgical and exercise stress, which may serve to prepare the host's immune defenses against trauma. The independent regulation of the DC and monocyte counts reinforces the distinction between these 2 cell populations.

Surgical and physical stress increases circulating blood dendritic cell counts independently of monocyte counts

Blood ◽  
2001 ◽  
Vol 98 (1) ◽  
pp. 140-145 ◽  
Author(s):  
Christopher S. K. Ho ◽  
Jose Alejandro López ◽  
Slavica Vuckovic ◽  
Christopher M. Pyke ◽  
Richard L. Hockey ◽  
...  
Keyword(s):  
The Body ◽  
Exercise Stress ◽  
Primary Immune Response ◽  
Cell Counts ◽  
Elective Laparoscopic Cholecystectomy ◽  
And Function ◽  
Antigen Presenting ◽  
Blood Dendritic Cell ◽  
Unique Ability

Abstract Dendritic cells (DCs) are specialized antigen-presenting cells that have the unique ability to initiate a primary immune response. The effect of physiologic stress on circulating blood DCs has thus far not been studied. In this study, we applied a recently developed method of counting blood DCs to test the hypothesis that significant stress to the body such as surgery and exercise might induce measurable changes in the DC numbers, subsets, phenotype, and function. Twenty-six patients scheduled for elective laparoscopic cholecystectomy, 4 for elective hysterectomy, 56 controls, and 5 volunteers who underwent a stress exercise test were enrolled in the study. Absolute DC counts increased acutely (71.7% ± 11% [SEM],P = .0001) in response to the stress of surgery and dropped below preoperative levels (−25% ± 14% [SEM],P = .05) on days 2-3. The perioperative DC subset balance remained constant. Interestingly, DC counts changed independently of monocyte counts. Exercise also induced a rise in DC counts but coincidentally with monocyte counts. Surprisingly, no phenotypic or functional activation of DCs was seen in either stress situations in vivo. DCs are rapidly mobilized into the circulation in response to surgical and exercise stress, which may serve to prepare the host's immune defenses against trauma. The independent regulation of the DC and monocyte counts reinforces the distinction between these 2 cell populations.

Anti-malarial drugs: possible mechanisms of action in autoimmune disease and prospects for drug development

Lupus ◽  
1996 ◽  
Vol 5 (1_suppl) ◽  
pp. 4-10 ◽  
Author(s):  
R Fox
Keyword(s):  
Immune Response ◽  
Cell Membrane ◽  
Mhc Molecules ◽  
Antimalarial Agents ◽  
Class Ii Mhc ◽  
Slight Elevation ◽  
Pass Through ◽  
Antigen Presenting

A wide variety of mechanisms of anti-rheumatic action have been proposed for antimalarial agents. The molecular actions of chloroquine have been most thoroughly studied in vitro and in vivo, but it is likely that hydroxychloroquine works by a similar mechanism. Both agents are weak diprotic bases that can pass through the lipid cell membrane and preferentially concentrate in acidic cyto-plasmic vesicles. The resulting slight elevation of pH within these vesicles in macrophages or other antigen-presenting cells may influence the immune response to autoantigens. We hypothesize that anti-malarial agents influence the association of autoantigenic peptides with class II MHC molecules in the compartment for peptide loading and/or the subsequent processing and transport of the peptide-MHC complex to the cell membrane. This model of anti-malarial action provides a method to test additional drugs for their ability to modulate the immune response.

scholarly journals Absence of complement component 3 does not prevent classical pathway–mediated hemolysis

2019 ◽  
Vol 3 (12) ◽  
pp. 1808-1814 ◽  
Author(s):  
Lingjun Zhang ◽  
Yang Dai ◽  
Ping Huang ◽  
Thomas L. Saunders ◽  
David A. Fox ◽  
...  
Keyword(s):  
Alternative Pathway ◽  
Membrane Attack Complex ◽  
Complement Component ◽  
Classical Pathway ◽  
In Vivo Experiments ◽  
Human Sera ◽  
Alternative Pathway Of Complement ◽  
Complement Component 3

Abstract Complement component 3 (C3) is emerging as a potential therapeutic target. We studied complement-mediated hemolysis using normal and C3-depleted human sera, wild-type (WT) and C3-deficient rat sera, and WT and C3 knockout rat models. In all of the in vitro and in vivo experiments, we found that the loss of C3 did not prevent classical pathway–mediated hemolysis, but it did almost abolish alternative pathway–mediated hemolysis. Experiments using preassembled classical pathway C3 convertases confirmed that C4b2a directly activated complement component 5 (C5), leading to membrane attack complex formation and hemolysis. Our results suggest that targeting C3 should effectively inhibit hemolysis and tissue damage mediated by the alternative pathway of complement activation, but this approach might have limited efficacy in treating classical pathway–mediated pathological conditions.

scholarly journals B Lymphocytes Regulate Dendritic Cell (Dc) Function in Vivo

2000 ◽  
Vol 192 (4) ◽  
pp. 475-482 ◽  
Author(s):  
Véronique Moulin ◽  
Fabienne Andris ◽  
Kris Thielemans ◽  
Charlie Maliszewski ◽  
Jacques Urbain ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Lymph Node ◽  
B Lymphocytes ◽  
Primary Immune Response ◽  
Wild Type ◽  
Helper Cell Type ◽  
Ifn Γ ◽  
Antigen Presenting

Increasing evidence indicates that dendritic cells (DCs) are the antigen-presenting cells of the primary immune response. However, several reports suggest that B lymphocytes could be required for optimal T cell sensitization. We compared the immune responses of wild-type and B cell-deficient (μMT) mice, induced by antigen emulsified in adjuvant or pulsed on splenic dendritic cells. Our data show that lymph node cells from both control and μMT animals were primed, but each released distinct cytokine profiles. Lymph node T cells from control animals secreted interferon (IFN)-γ, interleukin (IL)-2, and IL-4, whereas those from μMT mice produced IFN-γ and IL-2 but no IL-4. To test whether B cells may influence the T helper cell type 1 (Th1)/Th2 balance by affecting the function of DCs, we immunized mice by transferring antigen-pulsed DCs from wild-type or mutant mice. Injection of control DCs induced the secretion of IL-4, IFN-γ, and IL-2, whereas administration of DCs from μMT animals failed to sensitize cells to produce IL-4. Analysis of IL-12 production revealed that DCs from μMT mice produce higher levels of IL-12p70 than do DCs from wild-type animals. These data suggest that B lymphocytes regulate the capacity of DCs to promote IL-4 secretion, possibly by downregulating their secretion of IL-12, thereby favoring the induction of a nonpolarized immune response.

scholarly journals Localization of DNA damage and its role in altered antigen-presenting cell function in ultraviolet-irradiated mice.

1996 ◽  
Vol 183 (4) ◽  
pp. 1491-1500 ◽  
Author(s):  
A A Vink ◽  
F M Strickland ◽  
C Bucana ◽  
P A Cox ◽  
L Roza ◽  
...  
Keyword(s):  
Dna Damage ◽  
Uv Irradiation ◽  
Cell Function ◽  
Mouse Skin ◽  
Fluorescein Isothiocyanate ◽  
Antigen Presenting Cell ◽  
Exposed Skin ◽  
Pyrimidine Dimers ◽  
Antigen Presenting

Prior ultraviolet (UV) irradiation of the site of application of hapten on murine skin reduces contact sensitization, impairs the ability of dendritic cells in the draining lymph nodes (DLN) to present antigen, and leads to development of hapten-specific suppressor T lymphocytes. We tested the hypothesis that UV-induced DNA damage plays a role in the impaired antigen-presenting activity of DLN cells. First, we assessed the location and persistence of cells containing DNA damage. A monoclonal antibody specific for cyclobutyl pyrimidine dimers (CPD) was used to identify UV-damaged cells in the skin and DLN of C3H mice exposed to UV radiation. Cells containing CPD were present in the epidermis, dermis, and DLN and persisted, particularly in the dermis, for at least 4 d after UV irradiation. When fluorescein isothiocyanate (FITC) was applied to UV-exposed skin, the DLN contained cells that were Ia+, FITC+, and CPD+; such cells from mice sensitized 3 d after UV irradiation exhibited reduced antigen-presenting function in vivo. We then assessed the role of DNA damage in UV-induced modulation of antigen-presenting cell (APC) function by using a novel method of increasing DNA repair in mouse skin in vivo. Liposomes containing T4 endonuclease V (T4N5) were applied to the site of UV exposure immediately after irradiation. This treatment prevented the impairment in APC function and reduced the number of CPD+ cells in the DLN of UV-irradiated mice. Treatment of unirradiated skin with T4N5 in liposomes or treatment of UV-irradiated skin with liposomes containing heat-inactivated T4N5 did not restore immune function. These studies demonstrate that cutaneous immune cells sustain DNA damage in vivo that persists for several days, and that FITC sensitization causes the migration of these to the DLN, which exhibits impaired APC function. Further, they support the hypothesis that DNA damage is an essential initiator of one or more of the steps involved in impaired APC function after UV irradiation.

Anti-β2 Glycoprotein I Antibodies Cause Inflammation and Recruit Dendritic Cells in Platelet Clearance

2001 ◽  
Vol 86 (11) ◽  
pp. 1257-1263 ◽  
Author(s):  
Attilio Bondanza ◽  
Angelo Manfredi ◽  
Valérie Zimmermann ◽  
Matteo Iannacone ◽  
Angela Tincani ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Inflammatory Responses ◽  
Glycoprotein I ◽  
Activated Platelets ◽  
Tnf Α ◽  
Per Se ◽  
Antigen Presenting ◽  
Antiinflammatory Cytokine

SummaryScavenger phagocytes are mostly responsible for the in vivo clearance of activated or senescent platelets. In contrast to other particulate substrates, the phagocytosis of platelets does not incite pro-inflammatory responses in vivo. This study assessed the contribution of macrophages and dendritic cells (DCs) to the clearance of activated platelets. Furthermore, we verified whether antibodies against the β2 Glycoprotein I (β2GPI), which bind to activated platelets, influence the phenomenon. DCs did not per se internalise activated platelets. In contrast, macrophages efficiently phagocytosed platelets. In agreement with the uneventful nature of the clearance of platelets in vivo, phagocytosing macrophages did not release IL-1β, TNF-α or IL-10. β2GPI bound to activated platelets and was required for their recognition by anti-ββ2GPI antibodies. DCs internalised platelets opsonised by anti-ββ2GPI antibodies. The phagocytosis of opsonised platelets determined the release of TNF-α and IL-1β by DCs and macrophages. Phagocytosing macrophages, but not DCs, secreted the antiinflammatory cytokine IL-1β0. We conclude that anti-ββ2GPI antibodies cause inflammation during platelet clearance and shuttle platelet antigens to antigen presenting DCs.

Sign in / Sign up

Export Citation Format

Share Document