Whereas our present study clearly demonstrated mFPR2 to be
a proinﬂammatory immune response mediator, results ob-
tained using anti-inﬂammatory mFPR2 ligands have shown
protection of the host in some disease models. For example,
LXA4 and annexin I peptides signiﬁcantly reduced leukocyte
inﬁltration of airway tissues and type 2 responses in the airway
inﬂammation model (5). Clinically, the development of ex-
ercise-induced bronchoconstriction in asthmatic children was
linked to reduced biosynthesis of endogenous LXA4 (22).
However, it remains unclear how a single receptor such as
mFPR2 is capable of mediating opposing signaling events
elicited by different ligands. One possibility as suggested is
that anti-inﬂammatory ligands such as LXA4 may bind to
unique epitopes in mFPR2 (4). Alternatively, these ligands
may exhibit the property of partial agonists that desensitize,
and thus dampen, the proinﬂammatory function of mFPR2
or human FPR2 (1). In this context, although the chemical
nature of the mFPR2 agonist activity contained the in-
ﬂammatory BAL liquid remain s to be elucidated, our present
study has revealed a nonredundant role for mFPR2 in the
development of innate and adaptive immune responses rep-
resented by allergic airway inﬂammation.
We thank Dr. J.J. Oppenheim, Dr. O.M.Z. Howard, and Dr. G. Trinchieri for
critically reviewing the manuscript; C. Lamb for secretarial assistance; R. Mat-
thai and K. Noer of Center for Cancer Research (National Cancer Institute at
Frederick) for ﬂow cytometric analysis; and Steve Stull for bone marrow trans-
The authors have no ﬁnancial conﬂicts of interest.
1. Ye, R. D., F. Boulay, J. M. Wang, C. D ahlgren, C. Gerard, M. Parmentier, C. N.
Serhan, and P. M. Murphy. 2009. International Union of Basic and Clinical
Pharmacology. LXXIII. Nomenclature for the formyl peptide receptor (FPR)
family. Pharmacol. Rev. 61: 119–161.
2. Le, Y., P. M. Murphy, and J. M. Wang. 2002. Formyl-peptide receptors revisited.
Trends Immunol. 23: 541–548.
3. Gao, J. L., E. J. Lee, and P. M. Murphy. 1999. Impaired antibacterial host defense
in mice lacking the N-formylpeptide receptor. J. Exp. Med. 189: 657–662.
4. Chiang, N., I. M. Fierro, K. Gronert, and C. N. Serhan. 2000. Activation of lipoxin
A(4) receptors by aspirin-triggered lipoxins and select peptides evokes ligand-speciﬁc
responses in inﬂammation. J. Exp. Med. 191: 1197–1208.
5. Levy, B. D., G. T. De Sanctis, P. R. Devchand, E. Kim, K. Ackerman, B. A.
Schmidt, W. Szczeklik, J. M. Drazen, and C. N. Serhan. 2002. Multi-pronged
inhibition of airway hyper-responsiveness and inﬂammation by lipoxin A(4). Nat.
Med. 8: 1018–1023.
6. Lim, L. H., and S. Pervaiz. 2007. Annexin 1: the new face of an old molecule.
FASEB J. 21: 968–975.
7. Migeotte, I., E. Riboldi, J. D. Franssen, F. Gre
goire, C. Loison, V. Wittamer, M.
Detheux, P. Robberecht, S. Costagliola, G. Vassart, et al. 2005. Identiﬁcation and
characterization of an endogenous chemotactic ligand speciﬁc for FPRL2. J. Exp.
Med. 201: 83–93.
8. Yang, D., Q. Chen, B. Gertz, R. He, M. Phulsuksombati, R. D. Ye, and J. J.
Oppenheim. 2002. Human dendritic cells express functional formyl peptide re-
ceptor-like-2 (FPRL2) throughout maturation. J. Leukoc. Biol. 72: 598–607.
9. Devosse, T., A. Guillabert, N. D’Haene, A. Berton, P. De Nadai, S. Noel, M. Brait,
J. D. Franssen, S. Sozzani, I. Salmon, and M. Parmentier. 2009. Formyl
peptide receptor-like 2 is expressed and functional in plasmacytoid dendritic cells,
tissue-speciﬁc macrophage subpopulations, and eosinophils. J. Immunol. 182:
10. Gao, J. L., A. Guillabert, J. Hu, Y. Le, E. Urizar, E. Seligman, K. J. Fang, X. Yuan,
V. Imbault, D. Communi, et al. 2007. F2L, a peptide derived from heme-binding
protein, chemoattracts mouse neutrophils by speciﬁcally activating Fpr2, the low-
afﬁnity N-formylpeptide receptor. J. Immunol. 178: 1450–1456.
11. Holzenberger, M., C. Lenzner, P. Leneuve, R. Zaoui, G. Hamard, S. Vaulont, and
Y. L. Bouc. 2000. Cre-mediated germline mosaicism: a method allowing rapid
generation of several alleles of a target gene. Nucleic Acids Res. 28: E92.
12. Spangrude, G. J. 2001. Assessment of lymphocyte development in radiation bone
marrow chimeras. Curr. Protoc. Immunol. Chapter 4: Unit 4.6.
13. Duan, W., J. H. Chan, C. H. Wong, B. P. Leung, and W. S. Wong. 2004. Anti-
inﬂammatory effects of mitogen-activated protein kinase kinase inhibitor U0126 in
an asthma mouse model. J. Immunol. 172: 7053–7059.
14. Chen, K., P. Iribarren, J. Hu, J. Chen, W. Gong, E. H. Cho, S. Lockett, N. M.
Dunlop, and J. M. Wang. 2006. Activation of Toll-like receptor 2 on microglia
promotes cell uptake of Alzheimer disease-associated amyloid beta peptide. J. Biol.
Chem. 281: 3651–3659.
15. Aliberti, J., and A. Sher. 2002. Role of G-protein-coupled signaling in the induction
and regulation of dendritic cell function by Toxoplasma gondii. Microbes Infect. 4:
16. Lambrecht, B. N. 2005. Dendritic cells and the regulation of the allergic immune
response. Allergy 60: 271–282.
17. Stumbles, P. A., J. A. Thomas, C. L. Pimm, P. T. Lee, T. J. Venaille, S. Proksch,
and P. G. Holt. 1998. Resting respiratory tract dendritic cells preferentially stim-
ulate T helper cell type 2 (Th2) responses and require obligatory cytokine signals for
induction of Th1 immunity. J. Exp. Med. 188: 2019–2031.
18. Vermaelen, K. Y., I. Carro-Muino, B. N. Lambrecht, and R. A. Pauwels. 2001.
Speciﬁc migratory dendritic cells rapidly transport antigen from the airways to the
thoracic lymph nodes. J. Exp. Med. 193: 51–60.
19. Eisenbarth, S. C., D. A. Piggott, J. W. Huleatt, I. Visintin, C. A. Herrick, and K.
Bottomly. 2002. Lipopolysaccharide-enhanced, toll-like receptor 4-dependent
T helper cell type 2 responses to inhaled antigen. J. Exp. Med. 196: 1645–1651.
20. Pulendran, B., P. Kumar, C. W. Cutler, M. Mohamadzadeh, T. Van Dyke, and J.
Banchereau. 2001. Lipopolysaccharides from distinct pathogens induce different
classes of immune responses in vivo. J. Immunol. 167: 5067–5076.
21. Yang, D., Q. Chen, Y. Le, J. M. Wang, and J. J. Oppenheim. 2001. Differential
regulation of formyl peptide receptor-like 1 expression during the differentiation of
monocytes to dendritic cells and macrophages. J. Immunol. 166: 4092–4098.
22. Tahan, F., R. Saraymen, and H. Gumus. 2008. The role of lipoxin A4 in exercise-
induced bronchoconstriction in asthma. J. Asthma 45: 161–164.
The Journal of Immunology 3335