Lymphocyte/macrophage interactions: biomaterial surface-dependent cytokine, chemokine, and matrix protein production - PubMed (original) (raw)
Lymphocyte/macrophage interactions: biomaterial surface-dependent cytokine, chemokine, and matrix protein production
David T Chang et al. J Biomed Mater Res A. 2008.
Abstract
The role of lymphocytes in the biological response to synthetic polymers is poorly understood despite the transient appearance of lymphocytes at the biomaterial implant site. To investigate cytokines, chemokines, and extracellular matrix (ECM) proteins produced by lymphocytes and macrophages in response to biomaterial surfaces, human peripheral blood monocytes and lymphocytes were co-cultured on polyethylene terephthalate (PET)-based material surfaces displaying distinct hydrophobic, hydrophilic/neutral, hydrophilic/anionic, and hydrophilic/cationic chemistries. Antibody array screening showed the majority of detected proteins are inflammatory mediators that guide the early inflammatory phases of wound healing. Proteomic ELISA quantification and adherent cell analysis were performed after 3, 7, and 10 days of culture. IL-2 and IFN-gamma were not detected in any co-cultures suggesting lack of lymphocyte activation. The hydrophilic/neutral surfaces increased IL-8 relative to the hydrophobic PET surface (p < 0.05). The hydrophilic/anionic surfaces promoted increased TNF-alpha over hydrophobic and cationic surfaces and increased MIP-1beta compared to hydrophobic surfaces (p < 0.05). Since enhanced macrophage fusion was observed on hydrophilic/anionic surfaces, the production of these cytokines likely plays an important role in the fusion process. The hydrophilic/cationic surface promoted IL-10 production and increased matrix metalloproteinase (MMP)-9/tissue inhibitor of MMP (TIMP) relative to hydrophilic/neutral and anionic surfaces (p < 0.05). These results suggest hydrophilic/neutral and anionic surfaces promote pro-inflammatory responses and reduced degradation of the ECM, whereas the hydrophilic/cationic surfaces induce an anti-inflammatory response and greater MMP-9/TIMP with an enhanced potential for ECM breakdown. The study also underscores the usefulness of protein arrays in assessing the role of soluble mediators in the inflammatory response to biomaterials.
(c) 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2008.
Figures
Figure 1
(A) Macrophage/FBGC adhesion and (B) percent fusion from high monocyte co-cultures over 10 days. Data represents the mean ± standard error of the mean (SEM), n = 4. *Significance relative to PET (p < 0.05). ^Significance relative to BDEDTC (p < 0.05). #Significance relative to BDEDTC and DMAPAAmMeI (p < 0.05). †Significance relative to PET, BDEDTC, and DMAPAAmMeI (p <0.05).
Figure 2
IL-1β production from (A) low and (B) high monocyte co-cultures over 10 days. IL-6 production from (C) low and (D) high monocyte co-cultures over 10 days. TNF-α production from (E) low and (F) high monocyte co-cultures over 10 days. IL-10 production from (E) low and (F) high monocyte co-cultures over 10 days. Data represents the mean ± standard error of the mean (SEM), n = 4. *Significance relative to PAANa (p < 0.05). #Significance relative to PAAm and PAANa (p < 0.05). †Significance relative to PET, BDEDTC, and DMAPAAmMeI (p < 0.05).
Figure 3
IL-8 production from (A) low and (B) high monocyte co-cultures over 10 days. MIP-1β production from (C) low and (D) high monocyte co-cultures over 10 days. Data represents the mean ± standard error of the mean (SEM), n = 4. *Significance relative to PET (p < 0.05). †Significance relative to PET and BDEDTC (p < 0.05).
Figure 4
MMP-9 production from (A) low and (B) high monocyte co-cultures over 10 days. TIMP-1 production from (C) low and (D) high monocyte co-cultures over 10 days. TIMP-2 production from (E) low and (F) high monocyte co-cultures over 10 days. Data represents the mean ± standard error of the mean (SEM), n = 4. *Significance relative to PAAm (p < 0.05). †Significance relative to PAAm and PAANa (p < 0.05).
Figure 5
Ratio of MMP-9/TIMP-1 in co-cultures over (A) 3 days, (C) 7 days, and (E) 10 days. Ratio of MMP-9/TIMP-2 in co-cultures over (B) 3 days, (D) 7 days, and (F) 10 days. Data represents the mean ± standard error of the mean (SEM), n = 4. *Significance relative to PAAm (p < 0.05). †Significance relative to PAAm and PAANa (p < 0.05).
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